After oral administration of 0.8 g of bacampicillin, the median concentration of ampicillin in serum peaked at 1-2 hr and reached 8.4 and 12.3 micrograms/ml in two groups of 13 and four healthy volunteers, respectively. In the fluid of dermal blisters produced by suction, the peak values were 2.6 and 2.7 micrograms/ml, respectively. After oral administration of 1.6 g of bacampicillin to four healthy individuals, the median peak concentrations were 15.5 micrograms/ml in serum and 3.8 micrograms/ml in blister fluid. The rate of penetration of ampicillin into the blister fluid was lower than the rate of gastrointestinal absorption of bacampicillin, and the elimination of ampicillin from the blister fluid was slower than from serum; the half-life in blister fluid was approximately twice that in serum. Concentrations of ampicillin in the blister fluid exceeded those in serum at greater than or equal to 3 hr. Concentrations of less than 0.7 micrograms/ml were observed in blister fluid 11 hr after administration of the dose. The bioavailability of ampicillin was relatively greater after a 1.6-g dose of bacampicillin than after a 0.8-g dose. Inflammation in the blister fluid that was induced by endotoxin, which provoked a strong cellular response but cased no increase in the concentration of protein in the fluid, did not significantly influence the pharmacokinetics of ampicillin. The results suggest that the pharmacokinetics of antimicrobial agents in serum and in extravascular foci may be relevant to the setting of breakpoints between sensitivity and resistance of pathogens of antimicrobial agents.

Administration, Oral↗

PubMedDate not supplied

Penetration of antibiotics into human leukocytes and dermal suction blisters.

Staphylococcus aureus phagocytized by leukocytes from healthy donors and from patients with chronic granulomatous disease were protected from the antibacterial effect of gentamicin. Considerable numbers of phagocytized bacteria remained viable after exposure for 20 hr to antibiotic concentrations that killed greater than 99% of extracellular bacteria in less than 4 hr. A higher proportion of intracellular bacteria were killed by rifampin; this finding indicated that rifampin penetrates better into the phagocytic vacuole than does gentamicin and/or is more active against phagocytized bacteria than is gentamicin. After oral administration of 450 mg of rifampin to three healthy volunteers, concentrations of the antibiotic in serum and skin blister fluid were measured. Concentrations in serum peaked within 3 hr of oral administration (mean peak level, 13.2 micrograms/ml). Concentrations in blister fluid peaked between 6 hr and 9 hr (mean peak concentration, 2.7 micrograms/ml). Between 9 hr and 12 hr, the concentrations of rifampin in serum and blister fluid were similar; later, levels in blister fluid were higher than those in serum. The mean elimination half-life of rifampin was 2.5 hr in serum and 6.0 hr in blister fluid.

Adult↗