Dose-dependent absorption of amoxycillin and bacampicillin

Abstract

The relationship between the relative absorption and increasing oral doses of amoxycillin and bacampicillin, a prodrug of ampicillin, was studied testing the hypothesis that a saturable transport system for aminopenicillins exists in the human gut. Each drug was given in four different doses in a randomized order to 12 fasting subjects. One group of subjects was given amoxycillin in single doses of 375, 750, 1500, and 3000 mg, while the other group received bacampicillin in 400, 800, 1600, and 3200 mg doses. The highest dose was four times larger than that normally used in clinical practice. Amoxycillin, and ampicillin generated from bacampicillin, were determined in plasma and urine by modern column liquid chromatographic methods. With increasing doses of the penicillins, there was a saturable increase in peak plasma concentration, plasma AUC, and urinary recovery. The mean (+/- SD) AUC values after 750, 1500, and 3000 mg amoxycillin were 86% +/- 13%, 70% +/- 16%, and 55% +/- 14% of that expected, when the expected ratio of AUC to dose was that of the 375 mg dose, assuming nonsaturable absorption. The corresponding AUC values after 800, 1600, and 3200 mg bacampicillin were 97% +/- 17%, 89% +/- 19%, and 76% +/- 11% of that expected from the results obtained after the 400 mg dose. The importance of dose of either drug for AUC and urinary recovery was analyzed according to a function implying capacity-limited absorption. The dose-dependency was most pronounced for amoxycillin (P less than 0.001). Renal drug clearance was stable within subjects throughout the dose range. Our results support the concept of capacity-limited absorption of aminopenicillins, probably by carrier-mediated transport. However, limited solubility of the compounds, especially of bacampicillin, may be a confounding factor.

Intra‐ and inter‐individual variation in pharmacokinetics of intravenously infused amoxycillin and ampicillin to elderly volunteers.

“…Although there was a correlation between renal function and plasma clearance or renal clearance for ampicillin and amoxycillin, the plasma and renal clearances were essentially similar after amoxycillin and after ampicillin in this study compared to those previously reported in younger volunteers (Sjovall et al, 1985b) (Table 6). The mean fraction of the drug excreted unSlightly higher distribution volumes and changed in the urine was the same in these old plasma half-lives were seen in the elderly for subjects as in younger ones indicating a similar both drugs.…”

“…as these drugs are considered to be distributed (Sjovall et al, 1985b mainly to the extracellular fluid. A decrease in the volume of distribution with age is then expected, due to a decrease in the total body water with increasing age (Crooks et al, 1976).…”

“…) according to the principles previously described (Westerlund , 1979;Sjovall, et al, 1985a;Carlqvist & Westerlund, 1985). By this technique ampicillin was determined at 2-3 mg t1' plasma with an intra-assay precision of 0.9% (CV) and in urine at about 40 mg 1-1 with a precision of 1.4% (CV).…”

Low bioavailability of amoxicillin in rats as a consequence of presystemic degradation in the intestine

“…Most of this research has been carried out in rats on the basis of the assumption that rats represent suitable experimental animals for the elucidation of the absorption mechanisms of amino-plactam antibiotics in humans. From the results of those investigations, it has been suggested that saturable carrier-mediated transport is involved in the intestinal absorption of these antibiotics in rats (7,15), and the absorption features of amoxicillin in humans have sometimes been interpreted on the basis of such a mechanism (10,18). However, few investigators have assessed the suitability of using the rat as the animal model for studies of the bioavailability of amoxicillin (14) and other amino-1-lactam antibiotics after oral administration (2).…”

Use of an enzyme-linked immunosorbent assay to assess penetration of amoxicillin into lung secretions

“…The reasons for the difference between results obtained by Ingold (11) and those of the other studies, including those described here, are not clear since the procedures used in all these investigations were similar, with the exception of the study by Lovering and colleagues (17), in which the peak levels were observed following intravenous administration of the dose. The sputum pharmacokinetic data suggest that the delay in amoxicillin penetration into the lung secretions is about 0.5 to 2.5 h, since previous studies report that the peak level in serum in healthy fasting subjects is achieved 1.5 h after patients receive the drug (25,33). The predose sputum collection was made 8 h after the previous dose of amoxicillin.…”