Bacampicillin, Ampicillin, Cephalothin, and Cephapirin Levels in Human Blood and Interstitial Fluid

Abstract

The diffusibility of bacampicillin, ampicillin, cephalothin, and cephapirin into human interstitial fluid was investigated by using crossover studies. We compared bacampicillin with ampicillin and found that bacampicillin was better absorbed after oral administration. Blood, interstitial fluid, and urine levels were consistently higher in volunteers who received bacampicillin. We compared cephalothin with cephapirin and found that blood and interstitial fluid levels were comparable throughout the study. Bacampicillin versus ampiciflin. Six volunteers were given 1,600 mg of bacampicillin (equivalent to 1,112 mg of ampicillin), and six were given 2,000 mg of ampicillin. Both drugs were given by mouth after an 8-h fast. The study was repeated after 1 week, and the volunteers received the drug that they had not received previously.Cephalothin (Keflin neutral) versus cephapirin (Cefadyl). Six volunteers were given 1 g of one drug over a 30-min period by intravenous infusion, and six were given 1 g of the other drug. The study was repeated after 3 weeks. The volunteers received the drugs which they had not received previously.Blood samples. Venous blood was obtained before and 0.5, 1, 1.5, 2, 3, 4, and 5 h after administration of bacampicillin or ampicillin. The serum was separated after 45 min at 240C and immediately frozen. Venous blood was obtained before and 0.5, 1, 2, 3, and 4 h after the start of intravenous infusion of cephalothin or cephapirin. Blood was drawn into a heparinized tube to reduce deacetylation of the cephalosporins, and the plasma was separated and immediately frozen.Interstitial fluid samples. The technique of obtaining interstitial fluid by using a skin window chamber has been described previously (13).Urine sampling. Urine samples from six volunteers receiving bacampicillin and six receiving ampicillin were collected at 2, 4, and 5 h after antibiotic administration.Assay of antibiotics. Antibiotics were assayed by the agar well technique described by Bennett et al.(2), using a Bacillus subtilis spore suspension (Difco Laboratories, Detroit, Mich.) as the test organism. Pooled human plasma was used as the diluent for the standards of the serum and plasma antibiotic assay. Phosphate-buffered saline (pH 6) was used to dilute the standards for the skin window fluid assay. RESULTSBacampicillin versus ampicillin. The dose of bacampicillin administered was approximately half that of ampicillin, yet the serum antibiotic concentrations after the administration of bacampicillin consistently were higher during the first 3 h (Table 1). Similarly, the interstitial fluid levels of bacampicillin were also consistently higher. The serum and skin window fluid ratios were almost identical throughout the 5 h of the study.At the end of 5 h, volunteers who received ampicillin excreted in the urine an average of 492 mg of ampicillin, which is equivalent to 25% of the ingested dose. Volunteers who received bacampicillin excreted an average of 701 mg of ampicillin, which is equivalent to 63% of the ingested dose.Ceph...

Sulfonamide and trimethoprim concentrations in human serum and skin blister fluid

“…The penetration of antimicrobial agents to tissue fluid has been found by some authors to be inversely related to the degree of plasma protein binding (1,2,14). Others (5) have not been able to confirm this.…”

“…However, the skin blister technique does not require surgical intervention and is well tolerated. The skin window technique used by Tan and Salstrom (13,14) measures penetration into chambers filled with saline which is changed between each sample. The present method measures the drug penetration into blisters filled with the subject's own interstitial fluid.…”

“…Tan and Salstrom (13,14) used the ratio between mean tissue fluid and serum concentrations obtained simultaneously. Presumably the mean of such ratios from individual patients would be more appropriate.…”

“…Antibiotic penetration to tissue fluid has also been studied using tissue cages and skin abrasion techniques (1,2,5,13,14). The penetration of the drugs to tissue cages and skin blisters is slower than to the fluid sampled with the skin abrasion techniques (5,7).…”

Pharmacokinetics of β-Lactam Antibiotics

“…Although little is excreted in bile, biliary concentrations of ampicillin are comparable to those in serum, even in the presence of probenecid (STEWART and HARRISON 1961;AYLIFFE and DAVIES 1965;LUND et al 1974;KAMPMANN et al 1973;BROGARD et al 1977c). The area under the interstitial fluid level curve is comparable to that for serum and appears unaffected by lipopolysaccharide-induced inflammation (TAN et al 1974;BARZA and WEINSTEIN 1974;TAN and SALSTROM 1979;SCHREINGER et al 1978). Ampicillin readily crosses the synovial membrane with joint fluid concentrations approximating those in serum (HOWELL et al 1972).…”