Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers

Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum).In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC – THS (n = 22); Sequence 3: THS – Gum (n = 9); Sequence 4: Gum – THS (n = 9). Plasma nicotine concentrations were measured in 16 blood samples collected over 24 h after single use.Maximal nicotine concentration (C_max) and area under the curve from start of product use to time of last quantifiable concentration (AUC_0-last) were similar between THS and CC in both studies, with ratios varying from 88 to 104% for C_max and from 96 to 98% for AUC_0-last. Urge-to-smoke total scores were comparable between THS and CC.The THS nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to-smoke. This suggests that THS can satisfy smokers and be a viable alternative to cigarettes for adult smokers who want to continue using tobacco.     

The effect of variable cigarette consumption on the interaction with clozapine and olanzapine

Objective Cigarette smoking has been shown in several studies to induce the metabolism of the cytochrome P4501A2 (CYP1A2) substrates clozapine and olanzapine. The aim of the present study was to investigate the dose-dependent effect of cigarette smoking on serum concentrations of these drugs in a naturalistic setting.Methods In 73 schizophrenic patients recruited from psychiatric nursing homes, patient characteristics, smoking habits, drug dosing and serum concentrations of clozapine (n=33) and olanzapine (n=40) were registered. Concentration to dose (C/D) ratios of clozapine and olanzapine in non-smokers and subgroups of smokers were compared.Results Fifty-nine patients (80%) were smokers and these were stratified into the following groups according to smoking habits: 1–6 (n=0), 7–12 (n=13), 13–19 (n=18) and ≥20 (n=28) cigarettes daily. While the mean ratio was twice as high in non-smokers compared to smokers for both drugs (p<0.01), the C/D ratios of clozapine and olanzapine were not significantly different between the subgroups of smokers (p >0.15). Absolute serum concentrations were also higher in non-smokers compared to smokers: 50% for clozapine (p=0.058) and 67% for olanzapine (p<0.01).Conclusion A daily consumption of 7–12 cigarettes is probably sufficient for maximum induction of clozapine and olanzapine metabolism. A 50% lower starting dose of both drugs in non-smokers seems rational to avoid side effects.     

In Vivo Genotoxicity Assessment of Sertraline by Using Alkaline Comet Assay and the Cytokinesis‐Block Micronucleus Assay

Sertraline, a leading antidepressant in the selective serotonin reuptake inhibitor (SSRI) group of medicine, is the most frequently prescribed drug. In this study, the alkaline comet assay and the cytokinesis‐block micronucleus (CBMN) assay were used to investigate genotoxicity potential of sertraline in the peripheral blood lymphocytes (PBLs) of acute and chronic sertraline‐treated Wistar albino rats. Male Wistar albino rats (n = 48) were administered low, medium and high doses of sertraline (10, 40, 80 mg/kg) for acute and chronic treatment by employing the gavage method to investigate genotoxicity of the administered drug. The data (tail length, tail intensity and tail moment) were analysed and indicated that there was no statistically significant difference between sertraline‐treated groups and the negative control group with respect to DNA damage (p > 0.05). However, it was observed that acute sertraline administration had caused much more DNA damage in comparison with chronic treatment (p < 0.05). According to the data obtained from the CBMN test, an increase in the micronucleus (MN) frequency was detected at chronic and high‐dose acute sertraline treatment. Based on the outcome of comet assay, detection of statistically insignificant DNA damage may be due to the fact that sertraline did not cause damage on DNA. Also, increase in frequency of MN in chronic sertraline treatment suggests that chronic sertraline administration might influence some mechanisms of cell division. Therefore, dose adjustment in depressed patients seems significant as it may help prevent further prognosis of the diseases.     

Effects of active and passive smoking on the development of cardiovascular disease as assessed by a carotid intima‐media thickness examination in patients with type 2 diabetes mellitus

Carotid intima‐media thickness has been widely used as a surrogate end‐point for cardiovascular disease, myocardial infarction, and stroke. This study aimed to assess the effects of active and passive smoking exposure on the development of cardiovascular disease in patients with type 2 diabetes mellitus. Seven hundred twenty‐two patients with type 2 diabetes mellitus were recruited for the study. A standardized questionnaire on smoking status, pack‐years of smoking, and the number of years of smoking cessation was provided to the patients, and their responses were collected for analysis. The carotid intima‐media thickness, carotid plaque, and the internal diameter of the common carotid artery were determined by high‐resolution B‐mode ultrasonography. Compared to non‐smokers, passive female smokers had a higher risk of cardiovascular disease (odds ratio = 3.50, 95% confidence interval: 1.29–9.49, P = 0.009); they also had a significantly larger common carotid artery (P = 0.041) and risk of carotid plaque (odds ratio = 2.20, 95% confidence interval: 1.1980–4.0505, P = 0.01). Both active and passive male smokers had a significantly greater carotid intima‐media thickness than non‐smokers (P = 0.003 and P = 0.005, respectively). Male active smokers had a significantly higher risk of carotid plaque (odds ratio = 2.88, 95% confidence interval: 1.4788–5.6094, P = 0.001). In conclusion, cumulative active and passive smoking exposures are significant risk factors for carotid atherosclerosis in patients with type 2 diabetes mellitus. Our results highlight the importance of endorsing a smoke‐free environment for patients with type 2 diabetes mellitus.     

Genotype‐sensitive reversible and time‐dependent CYP2D6 inhibition in human liver microsomes

Cytochrome P450 (CYP) 2D6 metabolizes a wide range of xenobiotics and is characterized by a huge interindividual variability. A recent clinical study highlighted differential magnitude of CYP inhibition as a function of CYP2D6 genotype. The aim of this study was to investigate the effect of CYP2D6 genotype on the inhibition of dextromethorphan O‐demethylation by duloxetine and paroxetine in human liver microsomes (HLMs). The study focused on genotypes defined by the combination of two fully functional alleles (activity score 2, AS 2, n = 6), of one fully functional and one reduced allele (activity score 1.5, AS 1.5, n = 4) and of one fully functional and one non‐functional allele (activity score 1, AS 1, n = 6), which all predict extensive metabolizer phenotype. Kinetic experiments showed that maximal reaction velocity was affected by CYP2D6 genotype, with a decrease in 33% of V_max in AS 1 HLMs compared to AS 2 (P = 0.06). No difference in inhibition parameters K_i, K_I and k_inact was observed neither with the competitive inhibitor duloxetine nor with the time‐dependent inhibitor paroxetine. Among the genotypes tested, we found no difference in absolute CYP2D6 microsomal levels with ELISA immunoquantification. Therefore, our results suggest that genotype‐sensitive magnitude of drug‐drug interactions recently observed in vivo is likely to be due to differential amounts of functional enzymes at the microsomal level rather than to a difference in inhibition potencies across genotypes, which motivates for further quantitative proteomic investigations of functional and variant CYP2D6 alleles.     

Learning and memory performance following acute intranasal insulin administration in abstinent smokers

The highest incidence of relapse to smoking occurs within the first 2 weeks of a cessation attempt. In addition to enhanced nicotine craving, this phase of smoking cessation is also marked by learning and memory dysfunction. Many smokers are not able to overcome these symptoms, and they relapse to smoking shortly after trying to quit. In two clinical studies, we evaluated intranasal insulin for efficacy in improving learning and memory function during nicotine withdrawal. Our first study was a crossover evaluation (N = 19) following 20 hr of smoking abstinence. Study 2 was a parallel design study (N = 50) following 16 hr of abstinence. Intranasal insulin (60 IU) dose was administered in both studies and cognitive function was measured using California Verbal Learning Test‐II. Intranasal insulin did not improve learning over the 5 verbal learning trials. In addition, intranasal insulin did not improve either short‐ or long‐delay recall in either study. In summary, the one‐time administration of intranasal insulin does not improve verbal learning and memory in smokers. Whether longer administration schedules may be of benefit should be evaluated in future studies.     

Sex Difference in Formation of Propofol Metabolites: A Replication Study

Women recover faster from propofol anaesthesia and have been described to have a higher incidence of awareness during surgery, compared to men – an effect that may be inherent in sex differences in propofol metabolism. In an observational study, 98 ASA I‐II patients treated with continuous propofol infusion were recruited. The associations between sex and CYP2B6 and UGT1A9 polymorphisms with dose‐ and weight‐adjusted area under the total plasma level time curves (AUC) for propofol, and its metabolites propofol glucuronide (PG), 4‐hydroxypropofol (OHP) and hydroxyl glucuronide metabolites 4‐hydroxypropofol‐1‐O‐β‐D‐glucuronide (Q1G) and 4‐hydroxypropofol‐4‐O‐β‐D‐glucuronide (Q4G), were analysed. Significantly higher AUC of PG (1.3 times, p = 0.03), Q1G (2.9 times, p < 0.001), Q4G (2.4 times, p < 0.01) and OHP (4.6 times, p = 0.01) were found in women (n = 53) than in men (n = 45) after intravenous infusion of propofol using target‐controlled infusion system. There was, however, no significant impact of gene polymorphisms on propofol biotransformation. The results, which are supported by a previous pilot study using a propofol bolus dose, suggest that, compared to men, more rapid propofol metabolism may occur in women – a factor that may contribute to the mentioned differences in the efficacy of propofol anaesthesia between male and female patients.     

Plasma Levels of 25‐Hydroxyvitamin D3 and In Vivo Markers of Cytochrome P450 3A Activity in Swedes and Koreans: Effects of a Genetic Polymorphism and Oral Contraceptives

In vitro studies have shown that vitamin D may induce several cytochrome P450 (CYP) enzymes in general and CYP3A4 in particular. The primary aim of this study was to investigate the relationship between plasma levels of 25‐hydroxyvitamin D₃ and suggested in vivo markers of CYP3A activity in healthy volunteers from Sweden and Korea. Plasma concentrations of 25‐hydroxyvitamin D₃ were analysed in samples from three previously performed studies, and the correlation between these levels and suggested in vivo markers of CYP3A activity was investigated by means of nonparametric correlation. In addition, we studied the modulating effects of three vitamin D receptor promoter polymorphisms on the association between 25‐hydroxyvitamin D₃ and CYP3A enzyme activity in Swedish subjects. The plasma levels of 25‐hydroxyvitamin D₃ were not significantly associated with CYP3A phenotypes in any of the three studies, but after accounting for the vitamin D receptor polymorphism rs4516035, there was a significant positive association between 25‐hydroxyvitamin D₃ and CYP3A activity (p = 0.004). Swedes (n = 65) had significantly higher 25‐hydroxyvitamin D₃ levels than Koreans (n = 67), 75 nM compared with 31 nM (p < 0.001). Swedish women taking oral contraceptives (OC) (n = 19) had somewhat higher plasma levels of 25‐hydroxyvitamin D₃ compared with Swedish women not taking oral contraceptives (n = 21), 89 and 72 nM, respectively (p = 0.02). In conclusion, our results suggest that the overall influence on the CYP3A activity by 25‐hydroxyvitamin D₃ is of marginal importance.     

Pharmacokinetic and haemodynamic interactions between amlodipine and losartan in human beings

The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open‐label, three‐period, fixed‐sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP‐3174, an active metabolite of losartan, were assessed at steady‐state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady‐state (AUC_τ, 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954‐1.178)]. In addition, the exposure of EXP‐3174 was not affected by amlodipine (AUC_τ, 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891‐1.027]). However, amlodipine significantly decreased the exposure of losartan at steady‐state (AUC_τ, 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813‐0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co‐administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.     

Optimal teicoplanin loading regimen to rapidly achieve target trough plasma concentration in critically ill patients

Teicoplanin is used for the treatment of Methicillin‐resistant Staphylococcus aureus infection. It has been demonstrated that conventional loading regimen was insufficient for teicoplanin to achieve target trough plasma concentration (C_min > 10 mg/L). Therefore, a Chinese expert group recommended an optimal loading dose regimen of teicoplanin to treat severe Gram‐positive infection. However, there was no report about the teicoplanin concentration, and the safety and efficacy of teicoplanin therapy in Chinese patients since the consensus was published. The objective of this study was to compare the teicoplanin C_min and clinical response in critically ill Chinese patients after the administration of conventional or optimal loading regimen, and to reveal the potential factors that may affect teicoplanin C_min in addition to loading regimen. Fifty‐five patients were retrospectively divided into two groups based on teicoplanin loading regimen: (a) CD group (conventional loading dose group, n = 18, loading dose was 400 mg); (b) OD group (optimal loading dose group, n = 37, loading dose was 800 mg). Initially, three loading doses were administered every 12 hours, while the fourth loading dose was injected 24 hours after the third dose. The maintenance dose was 400 mg (CD group) or 800 mg (OD group), respectively. The mean teicoplanin C_min on day 2 and day 4 in the OD group was significantly higher than those in the CD group, which were 14.75 ± 5.93 mg/L vs 8.26 ± 4.87 mg/L (P < .001) and 14.90 ± 5.20 mg/L vs 9.13 ± 4.75 mg/L (P = .019), respectively. The percentages of patients in the OD group achieving the target teicoplanin C_min on day 2 and day 4 were also significantly higher than those in the CD group, which were 83.7% vs 33.3% (P < .001) and 82.4% vs 28.6% (P = .0013), respectively. Furthermore, multivariate linear regression analysis showed that body‐weight exerted significant effect on teicoplanin C_min in the OD group. The percentage of favourable clinical response in the OD group was significantly higher than that in the CD group (83.8% vs 55.6%, P = .025). There was no difference between teicoplanin adverse effects in the two groups. The study demonstrated that the optimal loading dose regimen of teicoplanin can rapidly reach target C_min, and result in a good clinical efficacy and low adverse effect in critically ill Chinese patients.     

The federal standard medication plan in practice: An observational cross-sectional study on prevalence and quality

BackgroundMedication plans are instruments used to document drug therapies, guide patients, and ensure medication safety. In Germany, patients who take at least 3 long-term medications are eligible to receive a medication plan. It has been statutory to use the federal standard layout (German: “Bundeseinheitlicher Medikationsplan”) since April 2017.ObjectivesThis study explores the prevalence, availability, medication discrepancies, and conformance with statutory regulations of medication plans since the introduction of the format of the federal standard medication plan in Germany.MethodsMedication reconciliation was performed for hospitalized patients according to the Best Possible Medication History principle. The collected medication lists were analyzed for medication discrepancies and conformance with the statutory regulations. The medication discrepancies were (1) omitted drugs, (2) additional drugs, and (3) dosing errors.ResultsAfter hospitalization, 524 patients taking drugs were included. The majority (n = 424 patients) were eligible for a medication plan. While 241 medication lists were present, only 24.1% (n = 58) matched the federal standard format. The mean number of drugs was 6.3 ± 3.6, with 3315 medications (3046 long-term and 269 as needed) reconciled totally. The 84 medication lists with omitted or additional drugs included 166 medication discrepancies upon 774 drugs listed. Of the 253 patients with dosing errors, 146 had a medication list. Inappropriate dosages were due to single dose (n = 195), daily dose (n = 225) or frequency of application (n = 255).ConclusionMedication plans are valuable tools for patients and health care providers. This study shows that the introduced paper-based federal standard medication plan in Germany falls short of its expectations regarding availability and correctness. Switching to an electronic patient record system may overcome some of the current pitfalls.     

Hormonal contraceptive use in smokers: Prevalence of use and associations with smoking motives

IntroductionWhile endogenous sex hormones influence smoking-related outcomes, little is known about the role of hormonal contraceptives (HCs). This is despite dated estimates suggesting that HC use is prevalent among female smokers. Therefore, we sought to update estimates of the prevalence of HC use among female smokers and explore the association of HC use with various smoking motives (SMs).MethodsThis online cross-sectional survey recruited female smokers between the ages of 18–35. Survey questions assessed smoking behavior, SMs, use of HCs, and menstrual cycle regularity.ResultsParticipants (n = 734) were, on average (± standard deviation), 20.7 ± 2.7 years old and smoked 7.3 ± 6.7 cigarettes/day. The majority of females reported a history of HC use (85%) and half reported current use (48%). Cyclical HC users (n = 227) scored significantly lower on three SMs compared to naturally-cycling women in the follicular phase (n = 62) and significantly higher on 15 SMs compared to naturally-cycling women in the luteal phase (n = 29). Women on cyclical HCs differed from women on long-acting HCs (n = 128) on two SMs. Further, the naturally-cycling women in the follicular phase scoring significantly higher on 15 SMs compared to those in the luteal phase.DiscussionThese observations indicate that HC use remains prevalent in female smokers and may influence SMs. Additional research should replicate these observations and explore the implications on smoking cessation outcomes.     

Sensitivity and Reliability of Halothane‐anaesthetized Microminipigs to Assess Risk of Drug‐induced Long QT Syndrome

Using moxifloxacin and terfenadine, which are known to induce benign and malignant QT interval prolongation, respectively, we analysed whether halothane‐anaesthetized microminipigs are an appropriate model for assessing the risk of drug‐induced long QT syndrome. Moxifloxacin (0.03, 0.3 and 3 mg/kg) and terfenadine (0.03, 0.3 and 3 mg/kg) were intravenously infused over 10 min. with a pause of 20 min. to the halothane‐anaesthetized microminipigs (n = 4 for each drug). Moxifloxacin decreased the heart rate, whereas it increased the blood pressure in a dose‐related manner. It also prolonged the PR interval and QT/QTc in a dose‐related manner without altering the QRS width. Terfenadine decreased the heart rate and blood pressure, whereas it prolonged the PR interval, QRS width and QT/QTc in a dose‐related manner. Terfenadine significantly prolonged the beat‐to‐beat variability of QT interval reflecting its pro‐arrhythmic potential, which was not observed with moxifloxacin. The peak plasma concentrations of moxifloxacin and terfenadine after doses of 3 mg/kg were 4.81 and 10.15 μg/mL, respectively, which were both 1.5 times less in microminipigs than those previously reported in dogs. These results indicate that halothane‐anaesthetized microminipigs would be useful for detecting drug‐induced cardiovascular responses as well as differentiating benign from malignant QT interval prolongation like dogs, although there may be some differences in pharmacokinetic profile between these animals.     

Serum 25‐Hydroxyvitamin D and Parathyroid Hormone Levels in Non‐Lactating Women with Post‐Partum Thyroiditis: The Effect of l‐Thyroxine Treatment

Vitamin D deficiency seems to be implicated in the onset and progression of some autoimmune disorders. No previous study has investigated vitamin D homeostasis in post‐partum thyroiditis. We compared 25‐hydroxyvitamin D and parathyroid hormone (PTH) levels between four groups of non‐lactating women who gave birth within 12 months before the beginning of the study: hypothyroid women with post‐partum thyroiditis (group A; n = 14), euthyroid females with post‐partum thyroiditis (group B; n = 14), women with non‐autoimmune hypothyroidism (group C; n = 16) and healthy euthyroid females without thyroid autoimmunity (group D; n = 15). In the second part of the study, groups A and C were treated for 6 months with l ‐thyroxine. Serum levels of 25‐hydroxyvitamin D were lower, while PTH higher in patients with post‐partum thyroiditis than in patients without thyroid autoimmunity. They were also lower (25‐hydroxyvitamin D) or higher (PTH) in group A than in group B, as well as in group C in comparison with group D. l ‐thyroxine treatment increased 25‐hydroxyvitamin D and reduced PTH levels only in hypothyroid women with post‐partum thyroiditis. Baseline levels of 25‐hydroxyvitamin D correlated with thyroid antibody titres, thyroid function and circulating PTH levels, while the effect of l ‐thyroxine on serum levels of this vitamin correlated with the changes in thyroid antibody titres and PTH levels. The results of our study suggest the association of vitamin D status with post‐partum thyroiditis and l ‐thyroxine treatment of this disorder.     

Renal pharmacists’ perceptions and current practices of assessing medication adherence in dialysis patients

Background Medication nonadherence is a major problem in chronic kidney failure patients undergoing dialysis. Pharmacists play a vital role in improving medication-related patient outcomes, reducing drug-related problems, and improving medication adherence. However, little is known about how pharmacists assess medication adherence in dialysis patients. Objective To measure pharmacists’ perceptions, current practices, and barriers to assessing adherence in dialysis patients. Setting Australian renal-specialised pharmacists. Method An online survey was conducted between March and May 2016. Survey included five psychometric scales measuring perceived prevalence, contributors, effective methods, barriers, and confidence to assess adherence on a 10-point Likert scale (1 = strongly disagree; 10 = strongly agree). Current practices were identified using a 4-point graded response (1 = do not practice; 4 = practice for all). Main outcome measure: Perception scores, scale reliability, and responses to current practices questionnaire. Results 41 pharmacists completed the survey (response rate, 91.1%). The majority (91.9%, n = 34; median = 8.0) agreed patients were nonadherent to medication. Time constraints (43.8%, n = 14) and hospital support (31.3%, n = 10) were perceived as barriers to assessment. Objective blood monitoring was frequently used to determine nonadherence (57.1%, n = 16), whereas subjective interviews were rarely conducted (27.6%, n = 8). Though all pharmacists support the presence of dedicated pharmacist for assessing adherence (100.0%, n = 33), only 24.2% were actually performing this function. Conclusion Pharmacists were rarely assigned for adherence assessment in dialysis settings. Established self-report methods were under-utilised compared to objective methods. Future research should investigate the effectiveness of pharmacists’ involvement in facilitating adherence promotion and early identification of medication-related issues in dialysis patients.

     

Pharmacist-led intervention aimed at deprescribing and appropriate use of cardiometabolic medication among people with type 2 diabetes

BackgroundPotential overtreatment with cardiometabolic medication (i.e., glucose lowering medication, antihypertensives and statins) has been observed in 10–40% of older people with type 2 diabetes (T2D).ObjectiveThe potential effects of a pharmacist-led clinical medication review targeted at T2D patients who were at high risk of hypoglycaemia will be investigated.MethodsA quasi-experimental study was conducted in 14 Dutch community pharmacies. Patients with a high risk of hypoglycaemia were identified using a previously developed algorithm. Pharmacists confirmed eligibility and selected patients for the intervention. Remaining eligible patients were included as controls receiving usual care. The primary outcome was the proportion of intervention patients for whom an action on deprescribing or appropriate use of cardiometabolic medication was implemented. After three months, changes in cardiometabolic medication were compared between the intervention and control group using a Fischer exact test.ResultsIn total 90 intervention patients and 107 control patients were included. Intervention patients had an average age of 70, used on average 10 medications, five of which were cardiometabolic medication. For half of the intervention patients an action on deprescribing cardiometabolic medication was implemented (n = 25) and/or an advice about appropriate use of cardiometabolic medication was given (n = 22). In 48% of intervention patients at least one cardiometabolic medication (e.g. insulin, sulfonylurea, diuretic, beta-blocker, statin) was either stopped or reduced in dose compared to 31% of control patients (p = 0.018).ConclusionsA pharmacist-led tailored clinical medication review has the potential to increase deprescribing and improve appropriate use of cardiometabolic medication in half of T2D patients at high risk of hypoglycaemia.     

Pharmacogenomics and Efficacy of Risperidone Long‐Term Treatment in Thai Autistic Children and Adolescents

The purpose of this study was to evaluate the association of pharmacogenomic factors and clinical outcome in autistic children and adolescents who were treated with risperidone for long periods. Eighty‐two autistic subjects diagnosed with DSM‐IV and who were treated with risperidone for more than 1 year were recruited. Pharmacogenomics and clinical outcome (CGI‐I, aggressive, overactivity and repetitive score) were evaluated. Almost all patients showed stable symptoms on aggressive behaviour (89.02%), overactivity (71.95%), repetitive (70.89%) behaviour and all clinical symptoms (81.71%). Only 4.48% of patients showed minimally worse CGI‐I score. Patients in the non‐stable symptom group had DRD2 Taq1A non‐wild‐type (TT and CT) frequencies higher than the clinically stable group (p = 0.04), whereas other gene polymorphisms showed no significant association. Haplotype ACCTCAT (rs6311, rs1045642, rs1128503, rs1800497, rs4436578, rs1799978, rs6280) showed a significant association with non‐stable clinical outcome (χ² = 6.642, p = 0.010). Risperidone levels showed no association with any clinical outcome. On the other hand, risperidone dose, 9‐OH risperidone levels and prolactin levels were significantly higher in the non‐stable compared to the stable symptom group (p = 0.013, p = 0.044, p = 0.030). Increased appetite was the most common adverse drug reaction and associated with higher body‐weight, whereas it was not significantly associated with genetic variations and non‐genetic information. In conclusion, risperidone showed efficacy to control autism, especially aggressive symptoms in long‐term treatment. However, Taq1A T – carrier of dopamine 2 receptor gene – is associated with non‐stable response in risperidone‐treated patients. This study supports pharmacogenomics testing for personalized therapy with risperidone in autistic children and adolescents.     

Alcohol and tobacco co‐use in nondaily smokers: An inevitable phenomenon?

Introduction and Aims. Alcohol use has consistently been associated with smoking among nondaily smokers. However, this may not be an inevitable relationship that extends across all drinking sessions and/or all nondaily smokers. Recently, distinct subgroups of nondaily smokers have been identified, with one subgroup maintaining a stable pattern of nondaily smoking (long‐term occasional smokers; LOS), and others transitioning to nondaily smoking either from a non‐smoking status (early occasional smokers; EOS) or from a daily smoking status (former daily smokers; FDS). However, little is known about the extent to which these subgroups differ in their alcohol–tobacco co‐administration patterns. Design and Methods. 183 nondaily smokers (74 LOS; 55 EOS; 54 FDS) completed face‐to‐face interviews during which they provided details about their lifetime and past‐week tobacco and alcohol administration patterns. Results. EOS were more likely to report having used alcohol at the time of their first‐ever cigarette relative to the other subgroups (P ≤ 0.001), but there were no differences in past‐week co‐administration patterns between the subgroups. Overall, less than one‐third of all smoking sessions occurred when drinking, but these accounted for more than half of all cigarettes consumed during the previous week. Moreover, while only 42% of drinking sessions involved tobacco co‐administration, when drinking and smoking did co‐occur, significantly greater amounts of alcohol were consumed relative to drinking sessions where no tobacco was used (P < 0.01). Discussion and Conclusions. Findings suggest that alcohol use is not invariably related to smoking in EOS, FDS or LOS, but when it is, across all subgroups co‐administration is associated with mutual dose escalation.[Campbell ML, Bozec LJ, McGrath D, Barrett SP. Alcohol and tobacco co‐use in nondaily smokers: An inevitable phenomenon? Drug Alcohol Rev 2012;31:447–450]