title: Evaluation of a novel method to estimate absolute bioavailability of drugs from oral data.
abstract: The goal of this investigation was to evaluate the performance of a novel method allowing estimation of absolute bioavailability from oral data only. In contrast to the traditional method, which compares areas under the drug concentration time curves after oral and intravenous administration in subjects with normal renal function, the novel method uses total and renal clearance values following oral administration from subjects with varying renal functions to estimate bioavailability. The novel method can also provide estimates for nonrenal clearance.Published data on total clearance and renal clearance of drugs obtained from subjects with variable renal functions were collected, the novel method applied, estimates of bioavailability and nonrenal clearance obtained and compared with reported estimates by the traditional methods. In addition computations were performed to assess various factors that could possibly affect the reliability of the novel method. The results indicated that the novel method provides accurate estimates for bioavailability of drugs meeting the prerequisites: linear kinetics, predominant renal excretion in normals, absence of metabolic polymorphism and independence of bioavailability and nonrenal clearance from renal function. The average (standard deviation) of the prediction error and bias of the bioavailability estimates by the novel method was 7.8 (6.0) and -1.4 (9.8)%, respectively. The estimates for nonrenal clearance by the novel method were less accurate. The computations confirmed that the estimates by the novel method are sensitive to renal-function dependent changes in nonrenal clearance and bioavailability and also depend on the extent of renal excretion of a drug. In conclusion, the novel method's main use is to diagnose absence or presence of changes in bioavailability and non-renal clearance of drugs in populations with varying renal function.
authors.affiliation: Berlex Laboratories, Inc, 340 Changebridge Road, Montville, NJ 07045, USA. hinderlingp@cder.fda.gov
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hinderling
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D016208:Databases, Factual / Q000706:statistics & numerical data*; D006801:Humans; D016014:Linear Models; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013223:Statistics as Topic
chemical_list: D004364:Pharmaceutical Preparations