Howard Weintraub

Drug distribution and pharmacologic effects

Drugs which move relatively slowly in and out of body “compartments” thereby confer pharmacokinetic characteristics of a multicompartment system and elicit a considerably different time course of pharmacologic effect than do drugs which are distributed in the body extremely rapidly. The time course of pharmacologiC effects in multicompartment systems is considered here as a function of dose and site of action and duration of repetitive dosings. The durationdose and intensity‐time patterns thus obtained are consistent with the results of clinical studies. An appreciation of these relationships should be helpful in designing effective and safe dosage regimens.

Comparative Bioavailability of Suprofen After Coadministration with Food or Milk

Suprofen is a nonsteroidal analgesic with demonstrated efficacy in the treatment of mild to moderate pain associated with a variety of clinical conditions. Because nonsteroidal analgesic agents may cause gastrointestinal side effects, they are frequently prescribed with food or milk. The purpose of this study was to evaluate the effects of a standard meal and milk alone on the rate and extent of absorption of suprofen. In a randomized three‐way cross‐over study, 24 healthy volunteers each received a single 200‐mg oral dose of suprofen in the fasted state half an hour after a standard meal or half an hour after an 8‐ounce glass of milk. The influence of food and milk was greater on the rate than on the extent of absorption of suprofen as illustrated by a more pronounced effect on Cmax than on AUC. In addition, food had a greater influence on the bioavailability of suprofen than milk. Food decreased the mean Cmax to 44% and the mean AUC to 81% relative to the fasted state, whereas milk decreased the mean Cmax to 74% and the mean AUC to only 87% of the respective parameters in the fasted state. Symmetrical confidence intervals demonstrated that the mean AUCmilk was within only 19% and the mean AUCfood was within only 25% of the mean AUC in the fasted state, with 95% confidence.