Cefaclor oral absorption

Equations (20) and (21) have been used to estimate the oral absorption of cefaclor, cefatrizine, and insulin. The simulated results compare favorably to the reported literature values in humans. The macroscopic mass balance approach provides a quick approximation to the fraction of dose absorbed and degraded for both passively and nonpassively absorbed drugs. 

Fewer cephalosporins have been of clinical interest for oral administration. Studies of cefatrizine (BLS-640 SKF 60771) (7) have continued to determine in vitro characteristics,65-67 human pharmacokinetics,66 68,69 and clinical effectiveness.69-71 Extensive clinical trial data documented the effectiveness of cefadroxil (BLS-578 -OH cephalexin).72 Cefaclor (Lilly 99638) ( ) has been shown in in vitro studies to have better activity than cephalexin against gram-negative bacteria, especially H. influenzae. 56 60 73 7 The excellent oral absorption in mice, rats, and dogs paralleled that of cephalexin.75 Metabolism was observed in dogs76 but not in rodents. Human pharmacology studies indicated that cefaclor gave acceptable blood and urine levels.77... 

Among the biological properties of cefaclor just reviewed, rapid oral absorption, metabolic stability, renal excretion, bactericidal activity, antimicrobial spectral characteristics, and low toxicity potential make this antibiotic an especially attractive candidate for use in the treatment of bacterial upper respiratory tract and urinary tract infections caused by susceptible bacteria. 

Cefaclor is well absorbed after oral administration. The presence of food may delay the absorption of cefaclor but the total amount absorbed remains unchanged. About 25 percent of the drug is protein bound. Cefaclor is widely distributed in the body. It is rapidly excreted by the kidneys, up to 85% appears unchanged in the urine within two hours. 

These results closely parallel those obtained with cephalexin in similar studies. In dogs, cefaclor is more labile to metabolism. Only a minor fraction of the administered dose is eliminated unchanged by the kidney. Total radiocarbon levels in both blood and urine were at considerably higher levels than could be present in unchanged antibiotic. As in the other species, biliary excretion in the dog plays only a minor role in the elimination of parent antibiotic and its metabolites (Sullivan et al., 1976). Other studies in the dog also showed rapid absorption of cefaclor following oral and intramuscular administration. Most of the dose was renally excreted, about 50% as intact antibiotic and the other 50% as microbiologically inactive degradation products. In the dog, cefaclor was shown to concentrate in the kidney and liver and to penetrate at lower levels into hard bone and synovial fluid (Quay et al., 1976). 

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