An Overview of the Analysis and Interpretation of Bioavailability Studies in Man

Wagner, Jutta

doi:10.1159/000136328

Cited by 25 publications

(13 citation statements)

References 3 publications

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“…All of a dose of cephradine appears to be excreted in the urine; presumably, cephradine is completely absorbed and eliminated completely by renal excretion. The total assayed cumulative urinary excretion of antibiotic in some subjects was greater than 100% of the dose, but the range of these recoveries did not exceed the 10 …”

Section: Methodsmentioning

confidence: 87%

Comparative Human Oral Clinical Pharmacology of Cefadroxil, Cephalexin, and Cephradine

Pfeffer

Jackson

Ximenes

et al. 1977

Antimicrob Agents Chemother

117

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At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephradine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadroxil is greater than that of cephalexin. These properties infer greater persistence of cefadroxil in serum and urine and more prolonged in vivo bacterial exposure to cefadroxil than to cephalexin or cephradine. Neither cefadroxil nor cephalexin demonstrates drug accumulation on repeated administration. The serum levels achieved by cefadroxil are unaffected by food. The pharmacokinetic properties of cefadroxil are supportive of the development of clinical efficacy data which could indicate that cefadroxil could be administered at 12-h intervals.The studies reported here were undertaken to compare the pharmacokinetic properties in humans of the orally administered cephalosporin antibiotics cefadroxil, cephalexin, and cephradine (structures presented in Fig. 1) and to determine the factors which control their disposition in vivo. A companion paper presents data on the antibacterial activity of cefadroxil (1). The inhibitory activity of cefadroxil on clinical isolates was similar to that of cephalexin and cephradine. Cefadroxil was more effective than cephalexin against Streptococcus pyogenes and comparably as effective as cephalexin against Streptococcus pneumoniae, Staphylococcus aureus, and several gram-negative species in oral treatment of experimental infections in mice. MATERIALS AND METHODSBioassays for antibiotic activity in serum and urine were carried out by standard cup plate assay methodology (4) blood area nitrogen, serum glutamic pyruvic transaminase, bilirubin, urinalysis (including protein test, sugar and microscopy for casts and cells), and stool parasitological examination. Subjects with abnormal values or findings were not admitted into these studies. None of the subjects were to have taken any medication for 3 weeks prior to the study in which they participated.All subjects were fasted overnight before each study. Oral doses of drugs were always administered at 8:00 a.m. with 250 ml of water, and a further 250 ml of water was ingested every succeeding 2 h for the duration of the study. Except for portions of a study on the effect of food on drug bioavailability, the subjects maintained their fast for 2 h after drug administration.All studies were designed as balanced, randomized complete crossovers. There was a 6-day washout period between crossover legs.Study

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Section: Methodsmentioning

confidence: 87%

Comparative Human Oral Clinical Pharmacology of Cefadroxil, Cephalexin, and Cephradine

Pfeffer

Jackson

Ximenes

et al. 1977

Antimicrob Agents Chemother

117

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“…Modern bioequivalence evaluation is enhanced with the biopharmaceutics drug classification system (BCS) (1) that was adopted as guidelines of BE by the Food and Drug Administration (FDA). Generally, the target entity in BA and BE studies is the parent drug; the comparison of the maximum plasma concentration (C max ) and the oral and intravenous area under the concentration-time profile (AUC from time zero to infinity) provide the rate and extent of absorption and oral bioavailability (2)(3)(4)(5), respectively. Riegelman and Rowland (6) and Rescigno (7) emphasized that BA cannot be determined by AUC ratios unless the AUC is proportional to the fraction absorbed and the clearance is constant.…”

Section: Introductionmentioning

confidence: 99%

Physiological Modeling to Understand the Impact of Enzymes and Transporters on Drug and Metabolite Data and Bioavailability Estimates

Sun

Pang

2010

Pharm Res

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“…It has been an axiom among pharmacologists that incompletely absorbed drugs are more variably absorbed than those whose absorption is complete, and that inter-and intrapatient variability in absorption, and therefore in therapeutic effect, should be minimized if possible. l !, 16,17,31 Such variability is particularly undesirable with a drug such as digoxin where the margin between therapeutic and toxic effects is narrow. We report here a series of studies of the comparative bioavailability of experimental digoxin preparations and standard tablets in human volunteers.…”

mentioning

confidence: 99%

Superior bioavailability of digoxin solution in capsules

Mallis

Schmidt

Lindenbaum

1975

Clin Pharma and Therapeutics

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The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers. Digoxin tablets that were 97% dissolved in 1 hr in vitro were not significantly better absorbed than tablets with a dissolution rate of 78%. A solution given in capsule form had greater bioavailability than tablets of 97% dissolution rate; serum and urinary glycoside levels after 0.4 mg doses of the encapsulated solution were similar to those attained after 0.5 mg doses of tablets with dissolution rates of 78% and 97%. The bioavailability of the solution in capsule form exceeded that of equal doses of the same solution given as a liquid or that of a standard elixir. No increase in gastrointestinal or cardiac toxicity was detected. Inter- and intrasubject variation in bioavailability was not decreased. Above a certain level, dissolution rate is no longer the limiting factor in digoxin absorption. The mechanism of the enhanced bioavailability of concentrated liquid digoxin in capsule form remains to be determined. Such a preparation deserves further consideration as a possible replacement for digoxin tablets.

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An Overview of the Analysis and Interpretation of Bioavailability Studies in Man

Cited by 25 publications

References 3 publications

Comparative Human Oral Clinical Pharmacology of Cefadroxil, Cephalexin, and Cephradine

Comparative Human Oral Clinical Pharmacology of Cefadroxil, Cephalexin, and Cephradine

Physiological Modeling to Understand the Impact of Enzymes and Transporters on Drug and Metabolite Data and Bioavailability Estimates

Superior bioavailability of digoxin solution in capsules

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