Annals of Pharmacotherapy

A case report of a possible interaction between indomethacin and warfarin is presented. The effect of warfarin on the prothrombin time (PT) was enhanced while indomethacin was given concurrently. Substitution of Ibuprofen for indomethacin resulted in the desired control of the prothrombin time.

Based on the results of controlled clinical trials and on the rarity of case reports, there is probably an extremely low incidence of enhancement of warfarin-induced hypoprothrombinemia by indomethacin.

Phenytoin serum levels were compared in a crossover study of a new 300 mg capsule form and three 100 mg capsules administered once daily. The new 300 mg capsule was equivalent to three 100 mg capsules in efficacy of seizure control and maintenance of phenytoin serum levels. This standard 300 mg dose produced a grand mean drug serum level of 7.63 mcg/ml and was below 10 mcg/ml in 15 to 20 patients. The authors recommend monitoring of phenytoin serum levels and clinical response, to detect needed dosage adjustments for optimum therapeutic benefit from phenytoin and to avoid toxic side effects.

A method to characterize the pharmacokinetics of a drug in a patient receiving it chronically is proposed. In principle, such characterization may be carried out by obtaining one or more drug concentration in plasma-time values from several different dosing intervals, combining the data to create a composite dosing interval representative of the steady-state situation and fitting the data to an appropriate equation. The method was evaluated using simulated data based on the average pharmacokinetic parameters of theophylline in children. Reasonable estimates of the elimination rate constant and apparent volume of distribution may be obtained, but the estimation of the absorption rate constant presents formidable problems. The method appears to be most useful for obtaining very accurate estimates of total clearance.