Effect of some drugs on penicillin half‐life in blood

Abstract

The half-life (T /2) of penicillin in blood was determined in 61 patients. An inverse relationship of penicillin T/2 and endogenous creatinine clearance was found. In a group of elderly patients with normal serum creatinine, penicillin T/2 was prolonged due to age-dependent decrease in renal function. The effect of several drugs on the active renal tubular transport mechanism of penicillin was studied. Probenecid increased penicillin T/2 from an average of 40.4 to 104.3 minutes. Penicillin T/2 in the younger patients using probenecid was of the same order as penicillin T/2 in elderly individuals not using probenecid. Phenylbutazone increased penicillin T/2 almost as much as did probenecid. Sulfinpyrazone, acetylsalicylic acid, indomethacin, and sulfaphenazole in therapeutic doses increased penicillin T /2 to a smaller degree. There was no significant change in penicillin T /2 after therapeutic doses of chlorothiazide, sulfamethizole, and sulfamethoxypyridazine.Recently a relationship between penicillin half-life ( T /2), glomerular filtration rate, and para-aminohippuric acid ( PAH) clearance was demonstrated. 12 Many acidic drugs are secreted by the same proximal tubular active transport mechanism as penicillin, but only probenecid and the phenylbutazones have been shown to reduce the rate of renal excretion of penicillin in man. 2 • 3 • 9 Lengthening the penicillin halflife might enhance the therapeutic effect, but it might also increase certain risksY This investigation was undertaken to study the relationship between penicillin T /2 in blood and age-dependent changes in renal

Mezlocillin Pharmacokinetics After Single Intravenous Doses to Patients with Varying Degrees of Renal Function

“…A lack of effect of concomitant J sulfamethoxazole-trimethoprim therapy on the 20 24 mezlocillin assay is supported by the absence of detectable antimicrobial activity after 8 h postof the mezlo-dosing in the patient receiving Septra. [2-g (0) and This study shows that the pharmacokinetic *g (A) dose], behavior of mezlocillin is, for the most part, similar to that of other penicillins (4,5,7,8,11). After intravenous dosage, the antibiotic distribtive to kid-utes initially into an apparent fluid volume replearance of resenting approximately 10% of body weight and nal impair-subsequently into a volume representing approxhable from imately 20% of body weight.…”

Effect of Tomanol® on the pharmacokinetics and tissue distribution of penicillin G in dairy cows

“…For example, the object of probenecid administration is to increase and to prolong serum drug concentrations or to achieve a longer persistence of beta-lactam antibodies in the urogenital tract. In the event of concomitant application of probenecid a decreased total body clearance and tissue distribution of beta-lactam antibiotics is assumed (4,5,10,15,16,17). For Bisolvon® higher chloramphenicol and oxytetracycline concentrations in bronchial and alveolar secretions are reported (1, 2).-In the human medical literature prolonging of biological half-lives and higher blood levels are reported after concomitant administration of acidic drugs like phenylbutazone, acetylsalicylic acid, sulfinpyrazone and Diflunisal® (10,12 The present study is concerned with the effect of Tomanol® on the pharmacokinetics of sodium penicillin G and the tissue distribution of (procaine) penicillin G in dairy cows.…”

Comparative Veterinary Pharmacokinetics

“…As active secretion plays an important role in the excretion of several substances, like most of the beta lactams, inhibiting the process significantly reduces elimination, thus increases half-life of these medicines. Probenecid, a substance inhibiting these carrier mediated transport mechanisms played an important role in prolonging the effect of penicillin (Kampmann et al, 1972).…”