A pharmacokinetic and pharmacodynamic comparison of plain and enteric-coated prednisolone tablets.

1. Eight healthy volunteers and eight patients suffering from chronic obstructive pulmonary disease (COPD) received 30 mg prednisolone as plain (P) and enteric-coated tablets (EP) in a randomised, cross-over manner. Plasma prednisolone and cortisol and blood glucose were measured over 24 h. 2. Although absorption of prednisolone was considerably slower when administered as the enteric-coated form, peak plasma drug concentrations and total AUC (0,24 h) were equivalent for the two formulations. Malabsorption of prednisolone was not observed. 3. The administration of EP was associated with significantly less adrenal suppression in volunteers than P as judged by measurement of AUC (0,24 h) values for endogenous cortisol. However, this difference did not reach statistical significance in the patient group. 4. Plasma cortisol concentrations declined more slowly following administration of the enteric-coated form to both groups. The difference in time taken (median and range) to maximum suppression of cortisol was statistically significant (P less than 0.05) between P (2.5 h; 2-4 h) and EP (4 h; 3-12 h) preparations administered to volunteers. There was a similar significant difference (P less than 0.05) between P (2.5 h; 1-4 h) and EP (7 h; 2-12 h) in the patients. 5. Plasma cortisol concentrations were significantly lower at 24 h in patients receiving the enteric-coated product in association with higher terminal prednisolone concentrations. 6. Blood glucose concentrations increased over an 8 h period in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of magnesium trisilicate and kaolin on the in vivo absorption of chloroquine

An in vitro study indicated that certain antacids and adsorbents may decrease the oral availability of th two widely used antimalarial agents chloroquine and pyrimethamine. To determine if this data was applicable to the clinical (in vivo) situation, plasma levels of one of the antimalarial agents (chloroquine) were followed in six Negro--Arab volunteers both when given alone and when taken with separate doses of two of the implicated interactants (magnesium trisilicate and kaolin). This in vivo work confirmed the in vitro findings; chloroquine area under the plasma concentration-time curve data were decreased by both magnesium trisilicate (18.2%) and kaolin (28.6%). Similar results could be expected for pyrimethamine. It is suggested therefore, to avoid loss of drug, that the antimalarials should not be taken with gastrointestinal medications of this type or that their administration should be separated by at least 4 h to reduce the risk of them interacting in the gut, thus preventing drug adsorption to the antacids/adsorbents, and loss of systemic availability.     

Pharmaceutical care programmes for the elderly: economic issues

Pharmaceutical care is defined as the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient's quality of life. It describes the process through which a pharmacist collaborates with a patient and with healthcare professionals in designing, implementing and monitoring a therapeutic plan that will produce specific, desirable therapeutic outcomes for the patient. The elderly are a patient population who could particularly benefit from pharmaceutical care provision as they are at greater risk of experiencing significant drug-related problems such as inappropriate prescribing, noncompliance with prescribed medication and adverse drug reactions/interactions leading to a decrease in health-related quality of life. The extent of economic benefit of pharmaceutical care reported in the literature is variable and its generalisability is suspect due to the lack of trials which have utilised a robust research design. The few studies which have undertaken a rigourous economic evaluation have used a range of data collection methods that is reflective of the difficulty of capturing essential data. Furthermore, even in well-designed studies, the generalisability of economic evaluations to other countries is questionable because of unique national data collection systems and an inability to pool international data because of disparities between different healthcare systems. The use of a suitable measure for health-related quality of life is also problematic in a very diverse and heterogeneous population such as the elderly and, therefore, adds to the difficulties of inclusion of such measures in economic analyses of pharmaceutical care programmes. A more standardised approach to data collection is required to facilitate economic analyses as an essential element in the evaluation of any pharmaceutical care programme for the elderly. Suggestions on such approaches, together with a critical appraisal of studies performed to date, are the focus of this review.     

Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

AIMS

The aim of this study was to investigate the influence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation.

METHODS

Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular filtration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes.

RESULTS

The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (≥30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls, P= 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%, P= 0.057). Carriers of the G2677->T variant allele also had a significant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P= 0.031). Haplotype analysis showed a significant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P= 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were significantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation.

CONCLUSIONS

These findings suggest that ABCB1 polymorphisms in the native intestine significantly influence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the first year post-transplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and enhance drug safety.     

Pharmaceutical care of patients with gestational diabetes mellitus

Rationale, aims and objective To investigate whether the introduction of a programme of optimising drug treatment, intensive education and self‐monitoring of patients diagnosed with gestational diabetes mellitus (GDM) at an early stage (<20 gestational weeks), will improve management outcomes as determined by objective measures of patient knowledge about diabetes, glycaemia control, maternal/neonatal complications, and health‐related quality of life. Methods The study was a randomized, controlled, longitudinal, prospective clinical trial performed at Al‐Ain Hospital, Al‐Ain, United Arab Emirates. Over an 18‐month period, patients diagnosed with GDM were recruited and were randomly assigned to either an intervention or a control group, in a ratio of 3:2. Intervention patients received a structured pharmaceutical care service (including education and introduction of intensive self‐monitoring) while control patients received traditional services. Patients were followed up from time of recruitment until 6 months postnatally at scheduled outpatient clinics. A range of clinical and humanistic outcome measures, including maternal and neonatal complications, were used to assess the impact of the intervention. Results A total of 165 patients (99 intervention, 66 control) completed the study. The intervention patients exhibited a range of benefits from the provision of the programme when compared with control group patients. Statistically significant (P < 0.05) improvements were shown in the intervention group for knowledge of diabetes, health‐related quality of life (as determined by the SF36), control of plasma glucose and HbA_1c, maternal complications [e.g. decreased incidence of pre‐eclampsia (5.1% vs. 16.7%), eclampsia (1.0% vs. 7.6%), episodes of severe hyperglycaemia (3.0% vs. 19.7%) and need for Caesarean section (7.1% vs. 18.2%)], and neonatal complications [e.g. decreased incidence of neonatal hypoglycaemia (2.0% vs. 10.6%), respiratory distress at birth (4.0% vs. 15.2%), hyperbilirubinaemia (1.0% vs. 12.1%) and large for gestational age (9.0% vs. 22.7%)]. Conclusion The research provides clear evidence that provision of pharmaceutical care adds value to the management of GDM as exemplified by improved maternal and neonatal outcomes.     

Sequential antimicrobial therapy: treatment of severe lower respiratory tract infections in children.

Although there have been a number of studies in adults, to date there has been little research into sequential antimicrobial therapy (SAT) in paediatric populations. The present study evaluates the impact of a SAT protocol for the treatment of severe lower respiratory tract infection in paediatric patients. The study involved 89 paediatric patients (44 control and 45 SAT). The SAT patients had a shorter length of hospital stay (4.0 versus 8.3 days), shorter duration of inpatient antimicrobial therapy (4.0 versus 7.9 days) with the period of iv therapy being reduced from a mean of 5.6 to 1.7 days. The total healthcare costs were reduced by 52%. The resolution of severe lower respiratory tract infection with a short course of iv antimicrobials, followed by conversion to oral therapy yielded clinical outcomes comparable to those achieved using longer term iv therapy. SAT proved to be an important cost-minimizing tool for realizing substantial healthcare costs savings.     

Development of a community pharmacy-based model to identify and treat OTC drug abuse/misuse: a pilot study

OBJECTIVE: The aim of this study was to develop and pilot a harm-minimisation model for the identification and treatment of over-the-counter (OTC) drug abuse/misuse by community pharmacists. METHOD: Extensive consultation was conducted during the development of the model. This included an exploratory conference involving an interdisciplinary group of delegates and detailed individual consultation with a range of healthcare practitioners. Consultation with a psychologist specialising in communication skills allowed development of the communication aspects of the model. A comprehensive manual detailing the model was prepared. RESULTS: The model is designed to be used by community pharmacists in conjunction with other healthcare professionals. It focuses on the abuse/misuse of opioids, laxatives and antihistamines and can be broadly divided into three phases, namely: patient identification and recruitment, treatment/referrals and data collection/outcome measurement. Client identification is via record-keeping which is implemented alongside an information campaign promoting safe use of OTC medicines. Once identified, the pharmacist aims to recruit clients using the developed communication strategies. Treatment depends on whether the problem is misuse or abuse and on the product. Several treatment paths are available including treatment according to an agreed protocol and referring to the GP or community addiction team (CAT). Two pharmacists were recruited and trained to pilot the model. Of the clients, 18 were identified as abusing/misusing OTC products over a one-month period. The subject of inappropriate OTC use was raised with 14 of these clients. Some success was noted in that clients agreed to stop using the product and/or to try safer alternatives. As expected, some sales had to be refused, as the client was unwilling to accept the pharmacist's intervention. CONCLUSION: This study represents the first reported structured attempt by community pharmacists in the UK to address the abuse/misuse of OTC medication. Work is now ongoing to modify this model in light of the pilot study findings.     

Metronidazole excretion in human milk and its effect on the suckling neonate.

1. Milk and plasma metronidazole and hydroxymetronidazole concentrations were measured in 12 breast-feeding patients following multiple doses of metronidazole (400 mg three times daily). All patients received metronidazole in combination with other broad spectrum antibiotics. 2. Plasma concentrations of both parent drug and metabolite were measured in seven suckling infants. Thirty-five infants were monitored for adverse reactions to maternal metronidazole therapy and two further groups of suckling infants, those whose mothers received either ampicillin alone or no drug therapy, were recruited as controls. 3. The mean milk to plasma ratio (M/P) was 0.9 for metronidazole and 0.76 for hydroxymetronidazole while the mean milk metronidazole concentrations (around Cmax) were 15.5 micrograms ml-1. The mean milk hydroxymetronidazole concentration was 5.7 micrograms ml-1. 4. Infant plasma metronidazole concentrations ranged from 1.27 micrograms ml-1 to 2.41 micrograms ml-1, and the corresponding hydroxymetronidazole concentrations from 1.1 to 2.4 micrograms ml-1. 5. There were no significant increases in adverse effects in infants which could be attributable to maternal metronidazole therapy. 6. Metronidazole was excreted in milk at concentrations which caused no serious reactions in the infants studied. The drug may therefore be administered at doses of 400 mg three times daily to mothers wishing to breast-feed their infants.