William R. Bartle

Dose‐dependent effect of cimetidine on phenytoin kinetics

Eight normal subjects were given 250 mg intravenous phenytoin alone and with 3‐day regimens of oral Cimetidine, 400 mg at bedtime, 1200 mg a day, and 2400 mg a day in a randomized crossover fashion. Plasma samples for phenytoin and Cimetidine, and urinary concentrations for phenytoin and 5‐(4‐hydroxyphenyl)‐5‐phenylhydantoin (HPPH) were measured by HPLC. All Cimetidine regimens decreased phenytoin clearance, and there was no difference between the 400‐mg bedtime dose and the 1200‐mg a day regimens. There was, however, a difference between the 400‐mg and 1200‐mg and the 2400‐mg regimens. There was no linear correlation between steady state Cimetidine plasma concentrations and the decrease in phenytoin clearance. Urinary HPPH/phenytoin ratios decreased with all Cimetidine treatments, but the differences were not significant. Phenytoin toxicity may result when Cimetidine is added to existing regimens of this anticonvulsant.

Rectal administration of propylthiouracil in the treatment of graves' disease

Rectal administration of propylthiouracil can be easily and rapidly achieved. The results of this case suggest that this can be an effective mode of therapy in patients in whom oral administration is impractical. Unfortunately, this case also demonstrates the seriousness of hyperthyroidism when an additional stress supervenes and the importance of appreciating the potential for thyroid storm

Interindividual and intraindividual variability in acetylation: Characterization with caffeine

The degree of interindividual and intraindividual variability in acetylator activity was investigated with caffeine used as a probe of enzyme activity. Acetylator phenotype and relative N‐acetyltransferase activity were estimated in 46 subjects by measuring the urinary ratio of two metabolites, AFMU/1‐MX, after a single 300 mg oral dose of caffeine on five separate occasions. Thirty homozygous slow (rr) and 15 heterozygous rapid (Rr) acetylators were identified. The degree of interindividual variability in acetylator activity was observed to be a mean of 32% (range 27% to 36%) and 20% (range 11% to 29%) in the rr and Rr groups, respectively. The mean intraindividual variation on repetitive measurement was 19% (range 6% to 49%) in the rr and 14% (range 7% to 24%) in the Rr acetylator group. Four subjects had apparent changes in acetylator activity with time such that they were unable to be assigned to any one acetylator group. Two of these four subjects exhibited apparent homozygous rapid acetylator activity intermittently during the 5‐week trial. This variability may explain, in part, some of the high degree of patient variability observed in the toxicity, efficacy, and drug‐related disease associated with acetylated drugs and environmental toxins.

Warfarin in the secondary prevention of thromboembolism in atrial fibrillation: impact of bioavailability on costs and outcomes.

AbstractBackground: The bioavailability of warfarin is an important factor affecting the achievement of therapeutic anticoagulation. It is uncertain whether less expensive generic preparations of warfarin would compromise prevention of thromboembolism or increase bleeding risk in patients with atrial fibrillation. Objective: To compare the cost effectiveness of strategies using warfarin products with variable bioavailability in patients with a prior stroke or transient ischaemic attack related to atrial fibrillation. Results: In our institution, warfarin F = 1 was similar in cost to the other three strategies (

Patient Information About Warfarin: An Assessment of Accuracy and Readability

Can1361 vs

Venous Thrombosis and the Pharmacist

Can1334–1613) and may be more effective than switching between generic preparations which have bioavailabilities at the extremes of acceptable limits (thromboembolism and bleeds 7. 1% vs 9.3%). Conclusions: In patients with atrial fibrillation and a prior ischaemic stroke or transient ischaemic attack, the use of one warfarin agent within the range of acceptable bioavailability can be considered economically attractive from the healthcare perspective.

Delayed Acetaminophen Toxicity despite Acetylcysteine Use

O ral vitamin K antagonists, such as warfarin, are among the most commonly prescribed and potentially dangerous classes of medications. For many high-risk drugs, such as warfarin, there is a strong link between patient knowledge about the medication and their safe use. For warfarin, provision of high-quality education improves compliance, increases time in the therapeutic range, and leads to a reduction in complications. Patients are largely educated about warfarin through written information sheets provided by their pharmacies. Therefore, it is critical that these sheets are both accurate and understandable. The objectives of this study were to assess the content (accuracy and completeness) and reading level of patient education sheets (PES) about warfarin provided to patients by community pharmacies in Ontario, Canada, and by pharmaceutical producers of this high-risk drug.