Eight healthy volunteers ingested an aqueous solution containing acetaminophen (20 mg/kg) and a nonabsorbable isotopic marker. The concentrations of unconjugated acetaminophen in samples of blood plasma taken at frequent intervals were measured by gas-liquid chromatography. The data points followed a smooth curve in most cases and were fitted to the classical two-compartment pharmacokinetic model to obtain K(a), the apparent first-order rate constant for absorption from the gastrointestinal tract. Gastric emptying was measured simultaneously from serial scintiscans of the subject's abdomen. The subjects were also studied after intramuscular injection of meperidine (150 mg) and pentazocine (60 mg) with and without naloxone (1.2 mg). The acetaminophen absorption curves and gastric emptying patterns were consistent with negligible absorption from the stomach. A new model is proposed in which the conventional single compartment used to represent the gastrointestinal tract is replaced by two compartments: one represents the stomach and the other the small intestine, from which absorption occurs rapidly. Pharmacokinetics analysis using this model showed good agreement in all cases, and provided an estimate of K(a), the first-order rate constant for drug transfer from the intestinal lumen into the systemic circulation. The mean half-time for transfer was 6.8 ± 0.9 min. As expected, K(a) was greater than K(g) (the first-order rate constant for gastric emptying), showing that gastric emptying was rate-limiting in the absorption of acetaminophen. The value of K(a) was greater than K(a) and the two were not related. The value of K(a) was not equal to K(g) in most studies because gastric emptying was not a single exponential process.
|Number of pages||12|
|Journal||Clinical Pharmacology and Therapeutics|
|Publication status||Published - 1978|