Incident opioid drug use among older adults with chronic obstructive pulmonary disease: a population‐based cohort study

Aims

The purpose of the present study was to describe the scope, pattern and patient characteristics associated with incident opioid use among older adults with chronic obstructive pulmonary disease (COPD).

Methods

This was a retrospective population‐based cohort study using Ontario, Canada, healthcare administrative data. Study participants were individuals aged 66 years and older with physician‐diagnosed COPD, identified using a validated algorithm, who were not receiving palliative care. We examined the incidence of oral opioid receipt between 1 April 2003 and 31 March 2012, as well as several patterns of incident opioid drug use.

Results

Among 107 109 community‐dwelling and 16 207 long‐term care resident older adults with COPD, 72 962 (68.1%) and 8811 (54.4%), respectively, received an incident opioid drug during the observation period. Among long‐term care residents, multiple opioid dispensings (8.8%), dispensings for >30 days'' duration (up to 19.8%), second dispensings (35–43%) and early refills (24.2%) were observed. Incident opioid dispensing was also observed to occur during COPD exacerbations (6.9% among all long‐term care residents; 18.1% among long‐term care residents with frequent exacerbations). These same patterns of incident opioid use occurred among community‐dwelling individuals, but with relatively lower frequencies.

Conclusions

New opioid use was high among older adults with COPD. Potential safety concerns are raised by the degree and pattern of new opioid use, but further studies are needed to evaluate if adverse events are associated with opioid drug use in this older and respiratory‐vulnerable population.     

Concomitant use of mirtazapine and cimetidine: a drug–drug interaction study in healthy male subjects

Objective: The objective of this study was to examine the pharmacokinetics and the tolerability/safety of mirtazapine and cimetidine separately and in combination following oral administration of multiple doses. Methods: This was a double-blind, placebo-controlled, two-period cross-over, multiple-dose pharmacokinetic interaction study in 12 healthy male subjects. They received either cimetidine (800 mg b.i.d.) or placebo in combination with (commercially available, racemic) mirtazapine (30 mg nocte). Cimetidine and placebo were administered for 14 days, with mirtazapine added during days 6–12 of each period. Serial blood samples for kinetic profiling were taken on day 5 and day 12 for cimetidine and on days 12–14 for mirtazapine. Results: The co-administration of cimetidine resulted in a statistically significant increase in the area under the curve (AUC_0–24) and C_max of mirtazapine (54% and 22% respectively). The AUC_0–24 of demethylmirtazapine increased only slightly, and there was no effect on C_max. The elimination half-lives for both mirtazapine and its demethyl metabolite were unaffected by cimetidine co-administration. The trough and average plasma concentrations during the steady state were elevated during cimetidine treatment (62% and 54%, respectively). Mirtazapine had no effect on the pharmacokinetics of cimetidine. Conclusion: Co-administration of cimetidine (800 mg b.i.d.) and mirtazapine (30 mg nocte) resulted in increased steady-state plasma levels of mirtazapine (C_ss,min= +61%, P < 0.05; C_ss,av=+54%, P < 0.05), probably as a result of increased bio-availability. The C_max (+22%, P < 0.05) and AUC_0–24 (+54%, P < 0.05) also increased. Due to the variability of the mirtazapine plasma levels in patients, the clinical meaning of these increases is probably limited. Co-administration of mirtazapine did not alter cimetidine pharmacokinetics. Received: 24 November 1999 / Accepted in revised form: 15 May 2000     

APOM‐project: a first study of pharmacy organization and management

In 1994, a Ph.D.study started regarding pharmacy, organization and management (APOM) in the Netherlands. The APOMproject deals with the structuring and steering of pharmacy organization. This article describes a summary of the theoretical background of the project and the empirical results of a pilot study (n=24). No generalization to the population of pharmacies in the Netherlands was made. Three mixes of objectives in pharmacy organization were theoretically postulated; the product mix, the process mix, and the customer mix. Mainly, the purpose of the pilot study was method selection. Additionally, it was studied if thought and action of pharmacy managers corresponded, and, if theoretical pharmacy mixes corresponded with the empirical pharmacy mixes. Two methods were selected to be applied in a survey. Thought and action did not correspond for most pharmacy managers. Thought related to customer and product mainly, and action related to process and customer mainly.     

Antimicrobial use and drug–drug interactions among nursing home residents in Singapore: a multicentre prevalence study

Background With the Ministry of Health’s projected increase in nursing home beds and optimization of antimicrobial use in health care settings, it is therefore timely to consider baseline prevalence and patterns of antimicrobial use at nursing homes in Singapore as well as to evaluate the prevalence of potential clinically significant drug–drug interactions involving antimicrobials. Objective The primary objective was to determine the prevalence and patterns of antimicrobial use at nursing homes in Singapore. The secondary objective was to evaluate the prevalence of potential clinically significant drug–drug interactions involving antimicrobials. Setting Four nursing homes in Singapore. Method A retrospective cross-sectional study was conducted among nursing home residents. The antimicrobial prevalence, defined daily doses, days of therapy, and potential drug–drug interactions were determined using data from archived resident medication prescribing and administration records. Main outcome measure Prevalence and patterns of antimicrobial use, drug–drug interactions involving antimicrobials. Results Among 707 residents (mean age: 80.7?±?8.8 years, female: 57.1%), 10% used antimicrobials during the study month, with a 1-day point prevalence of 3%. The utilization rates of antimicrobials were 28.9 defined daily doses/1000 resident-days and 24.8 days of therapy/1000 resident-days. Potential drug–drug interactions involving antimicrobials were identified among 32 of the 70 (46%) residents who were prescribed antimicrobials. Of these, 26 (81%) residents had 43 potential clinically significant drug–drug interactions. Conclusions The prevalence and utilization rates of antimicrobial use in Singapore nursing homes appear to be low. Yet, potential clinically significant drug–drug interactions are prevalent.     

Retrospective use of PBPK modelling to understand a clinical drug–drug interaction between dextromethorphan and GSK1034702

1.?In a clinical trial, a strong drug–drug interaction (DDI) was observed between dextromethorphan (DM, the object or victim drug) and GSK1034702 (the precipitant or perpetrator drug), following single and repeat doses. This study determined the inhibition parameters of GSK1034702 in vitro and applied PBPK modelling approaches to simulate the clinical observations and provide mechanistic hypotheses to understand the DDI.

2.?In vitro assays were conducted to determine the inhibition parameters of human CYP2D6 by GSK1034702. PBPK models were populated with the in vitro parameters and DDI simulations conducted and compared to the observed data from a clinical study with DM and GSK1034702.

3.?GSK1034702 was a potent direct and metabolism-dependent inhibitor of human CYP2D6, with inhibition parameters of: IC_50?=_?1.6?μM, K_inact?=?3.7?h^?1 and K_I?=?0.8?μM. Incorporating these data into PBPK models predicted a DDI after repeat, but not single, 5?mg doses of GSK1034702.

4.?The DDI observed with repeat administration of GSK1034702 (5?mg) can be attributed to metabolism-dependent inhibition of CYP2D6. Further, in vitro data were generated and several potential mechanisms proposed to explain the interaction observed following a single dose of GSK1034702.     

The ICPC coding system in pharmacy: developing a subset. ICPC‐Ph.

The ICPC system is a coding system developed for general medical practice, to be able to code the GPpatient encounters and other actions. Some of the codes can be easily used by community pharmacists to code complaints and diseases in pharmaceutical care practice. We developed a subset of the ICPC codes for community pharmacists. This article describes the method used and the resulting ICPCPh list.     

“How do online and offline sampling compare in a multinational study of drug use and nightlife behaviour?”

BackgroundOnline sampling is widely used to recruit hard to reach samples such as drug users at nightlife events. We conducted the first study comparing differences in demographics, drug use and nightlife behaviour between an online sample of young adults engaging with the European nightlife scene, and an offline sample recruited at nightclubs and festivals in Europe.MethodsOnline participants who attended at least six nightlife events in the past 12 months were recruited using social media advertising (May-November 2017). Offline participants were recruited at nightclubs and festivals using a random intercept method (May-November 2017). Samples were compared with respect to age, gender, past year use of alcohol, cannabis, cocaine, ecstasy/MDMA and amphetamines, and past year attendance at nightclubs, licensed festivals, illegal festivals, pubs and house-parties.Results6153 online and 3529 offline participants were recruited. When adjusting for differences in age and gender, online participants were less likely to have used each drug and to have attended illegal festivals, pubs and house-parties in the past 12 months. The online sample also used each drug and attended each venue, with the exception of nightclubs, less frequently on average than offline participants. Adjusted odds ratios (range 0.37 to 1.39) and regression coefficients (range -0.84 to 0.07) indicate that the majority of observed differences between the samples were of a small effect size.ConclusionsEstimates of drug use and nightlife engagement are more conservative when using online sampling compared to venue based sampling. Observed differences were generally small in effect, indicating good overall representativeness when using online sampling in the European nightlife scene.     

Comparison of two endogenous biomarkers of CYP3A4 activity in a drug–drug interaction study between midostaurin and rifampicin

Purpose

Midostaurin, a multitargeted tyrosine kinase inhibitor, is primarily metabolized by CYP3A4. This midostaurin drug–drug interaction study assessed the dynamic response and clinical usefulness of urinary 6β-hydroxycortisol to cortisol ratio (6βCR) and plasma 4β-hydroxycholesterol (4βHC) for monitoring CYP3A4 activity in the presence or absence of rifampicin, a strong CYP3A4 inducer.

Methods

Forty healthy adults were randomized into groups for either placebo or treatment with rifampicin 600 mg QD for 14 days. All participants received midostaurin 50 mg on day 9. Midostaurin plasma pharmacokinetic parameters were assessed. Urinary 6βCR and plasma 4βHC levels were measured on days 1, 9, 11, and 15.

Results

Both markers remained stable over time in the control group and increased significantly in the rifampicin group. In the rifampicin group, the median increases (vs day 1) on days 9, 11, and 15 were 4.1-, 5.2-, and 4.7-fold, respectively, for 6βCR and 3.4-, 4.1-, and 4.7-fold, respectively, for 4βHC. Inter- and intrasubject variabilities in the control group were 45.6 % and 30.5 %, respectively, for 6βCR, and 33.8 % and 7.5 %, respectively, for 4βHC. Baseline midostaurin area under the concentration–time curve (AUC) correlated with 4βHC levels (ρ?=??0.72; P?=?.003), but not with 6βCR (ρ?=?0.0925; P?=?.6981).

Conclusions

Both 6βCR and 4βHC levels showed a good dynamic response range upon strong CYP3A4 induction with rifampicin. Because of lower inter- and intrasubject variability, 4βHC appeared more reliable and better predictive of CYP3A4 activity compared with 6βCR. The data from our study further support the clinical utility of these biomarkers.     

Formulation and in vitro/in vivo correlation of a drug‐in‐adhesive transdermal patch containing azasetron

The aim of the present study was to develop a transdermal drug delivery system for azasetron and evaluate the correlation between in vitro and in vivo release. The effects of different adhesives, permeation enhancers, and loadings of azasetron used in patches on the penetration of azasetron through rabbit skin were investigated using two‐chamber diffusion cells in vitro. For in vivo studies, azasetron pharmacokinetic parameters in Bama miniature pigs were determined according to a noncompartment model method after topical application of transdermal patches and intravenous administration of azasetron injections. The best permeation profile was obtained with the formulation containing DURO‐TAK 87‐9301 as adhesive, 5% of isopropyl myristate as penetration enhancer, and 5% of azasetron. The optimal patch formulation exhibited sustained release profiles in vivo for 216 h. The in vivo absorption curve in Bama miniature pigs obtained by deconvolution approach using WinNonlin® program was correlated well with the in vitro permeation curve of the azasetron patch. These findings indicated that the developed patch for azasetron is promising for the treatment of delayed chemotherapy‐induced nausea and vomiting, and the in vitro skin permeation experiments could be useful to predict the in vivo performance of transdermal azasetron patches. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4540–4548, 2012     

Borderline intellectual functioning is associated with poor social functioning,increased rates of psychiatric diagnosis and drug use – A cross sectional population based study

Borderline intellectual functioning is defined by the DSM IV as an IQ range that is between one to two standard deviations below the mean (71<IQ<84), and a considerable percentage of the population is included in this definition (approximately 13.5%). The few studies performed on this group indicate that borderline intellectual functioning is associated with various mental disorders, problems in everyday functioning, social disability and poor academic or occupational achievement. Using data from the Israeli military, we retrieved the social and clinical characteristics of 76,962 adolescents with borderline intellectual functioning and compared their social functioning, psychiatric diagnoses and drug abuse with those of 96,580 adolescents with average IQ (±0.25 SD from population mean). The results demonstrated that the borderline intellectual functioning group had higher rates of poor social functioning compared to the control group (OR=1.9, 95% CI=1.85–1.94). Individuals with borderline intellectual functioning were 2.37 times more likely to have a psychiatric diagnosis (95% CI=2.30–2.45) and 1.2 times more likely to use drugs (95% CI=1.07–0.35) than those with average IQ. These results suggest that adolescents with borderline intellectual functioning are more likely to suffer from psychiatric disorders, poor social functioning and drug abuse than those with average intelligence, and that borderline intellectual functioning is a marker of vulnerability to these poor outcomes.     

Dose-effect relationships of intravenous enoxaparin in patients undergoing percutaneous coronary intervention：a population and bayesian approach based study

AIM: Recent studies have suggested that intravenous enoxaparin can be used as an alternative therapy in patients percutaneous coronary intervention (PCI); yet the optimal regimen is to be defined. METHODS: Anti-Xa activities were measured in 556 patients who received a single 0.5 mg/kg dose of enoxaparin intravenously immediately before PCI. A population pharmacoki-