Nonlinear Regression Approach for Determining Whether Absorption and Elimination Rate Constants are Equal in the One-Compartment Open Model with First-Order Processes

1 The excretion of antipyrine metabolites over 48 h as percentage dose and the antipyrine kel and metabolite formation rate constants have been measured for 20 healthy Venda Africans. 2 To allow comparison with published data from inter-ethnic studies with antipyrine, subjects were selected who had assumed a western life and diet. 3 The values (mean ± SE) for excretion of the metabolites, 4-hydroxyantipyrine (4OHA), norantipyrine (NORA) and 3-hydroxymethylantipyrine (3HMA) as percentage dose were 26.17 ± 0.34, 7.44 ± 0.34 and 13.28 ± 0.31 respectively. The total of the three metabolites was 49.56 ± 0.33. These results differ significantly from the values found for groups of Canadian students of Oriental and Caucasian backgrounds. 4 The values (mean ± SE) found for the antipyrine elimination rate constant and the metabolite formation rate constants of 4OHA, NORA and 3OHA were 6.56 (± 0.56) × 10 -2, 2.05 (± 0.24) x 10-2, 0.60 (± 0.09) x 10-2 and 1.06 (± 0.16) x 10-2 respectively. Only the NORA formation rate constant showed any significant difference with the results obtained for Americans, although the Venda exhibited a wider distribution of the 3HMA data. 5 The linearity of the probit plots obtained suggest that the subjects selected are homozygous for the oxidations investigated. The marked difference found in comparison with Caucasian and Oriental data on the one hand and American data on the other, also implies a marked difference between the Caucasian and Oriental data and the American data. Thus the relative contributions of environmental induction and heredity to these types of oxidation are still unclear and much work remains to be carried out in this field.

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Erratum to: Simplified methods for the evaluation of the parameters of the time course of plasma concentration in the one-compartment body model with first-order invasion and first-order drug elimination including methods for ascertaining when such rate constants are equal

Journal of Pharmacokinetics and Biopharmaceutics ◽

10.1007/bf02353543 ◽

1994 ◽

Vol 22 (2) ◽

pp. 179-179

Author(s):

Edward R. Garrett

Keyword(s):

Plasma Concentration ◽

Rate Constants ◽

Time Course ◽

Drug Elimination ◽

First Order ◽

Body Model ◽

The One

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Pharmacokinetic Predictions Based on a Variable Dosage Frequency in Chronic Treatment

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808301700413 ◽

1983 ◽

Vol 17 (4) ◽

pp. 290-292 ◽

Cited By ~ 3

Author(s):

Andrea Messori ◽

Giancarlo Donati-Cori ◽

Enrico Tendi

Keyword(s):

Oral Administration ◽

Chronic Treatment ◽

Plasma Drug ◽

Programmable Calculator ◽

Open Model ◽

Dosing Interval ◽

Drug Levels ◽

First Order ◽

Compartment Open Model ◽

Dosage Frequency

After repeated intramuscular or oral administration, plasma drug levels are predicted by using a programmable calculator. Predictions are based on a one-compartment, open model with first-order absorption. The actual times of dosing are considered, so that the assumption of a constant dosing interval is not required. A brief analysis of the pharmacokinetic consequences that may result from a variable dosage frequency is presented.

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