A standard approach to compiling clinical pharmacokinetic data

Abstract

A standard format for a Clinical Pharmacokinetic Summary is proposed. It consists of a heading, tables, notes, and references for each drug reviewed. The table presents a unified and logical set of clinically useful population pharmacokinetic parameters. They concern four major areas: absorption, distribution, elimination, and the relationship of concentration to effect. Within each major group, parameters dealing with extents and rates of processes are given. Each such parameter is really two: a population mea value (for example, average volume of distribution) and the standard deviation of individual values about this mean. The first value allows individual predictions of dosage or drug level to be made; the second allows computation of the likely proximity of subsequently observed quantities to those predictions. The table presents single consensus values for each population parameter, rather than a list of values. A procedure for computing these consensus values, and for revising them in the light of new data, or reinterpreted old data, is given. Examples of Summaries are given. The method appears applicable to a variety of drugs. We suggest our approach as a standard one for preparing Clinical Pharmacokinetic Summaries, and urge our colleagues to consider it for that purpose.

Discrepancies Between Pharmacokinetic Studies of Amitriptyline

“…The importance of these methodological issues is illustrated by the numerous, statistically significant differences in mean parameter values between separate studies. The method proposed by Sheiner et al (1981) for pharmacokinetic summaries includes some correction for potential bias and is very suitable for integrating the data on amitriptyline. Table V contains all pertinent and major information from tables II to IV.…”

“…The objective was to produce a single table that would provide a complete and critically assessed list of the pharmacokinetic and pharmacodynamic parameters of any drug. Because of insufficient data for amitriptyline, not all headings in the original paper of Sheiner et al (1981) could be included. Additional information is listed in table V, such as the distribution of amitriptyline or nortriptyline among the constituents of blood.…”

“…use of Vacutainers, late sampling, non-compliance) should have increased the calculated values for amitriptyline CLa. Table V is a summary of the pharmacokinetic studies, which utilises a form of presentation proposed by Sheiner et al (1981). The objective was to produce a single table that would provide a complete and critically assessed list of the pharmacokinetic and pharmacodynamic parameters of any drug.…”

Effect of itraconazole on the pharmacokinetics of digoxin in guinea pigs

“…On the other hand, DGX was reported in man to be excreted largely in urine as the unchanged form after iv administration of DGX, and its urinary recovery was 60 -80% [14,15]. Sheiner et al [16] reported that the total body, renal and metabolic clearances of DGX were 2.909 1.0, 1.64 90.50 and 0.79090.460 mL/min/kg (mean9…”

Pediatric Clinical Pharmacology Studies in Chagas Disease

“…The study is being conducted according to number of individuals is required to participate, but the amount of the guidelines of the International Conference on Harmonization samples per individual is greatly reduced (to as few as two samples (ICH6), Good Clinical Practice guidelines (GCP), the declaration in some study designs). [50][51][52][53][54][55] This milder burden on the individual of Helsinki, the UNICEF convention on the rights of children, and patient makes population pharmacokinetics the ideal choice for the regulations of the ANMAT. studies in children.…”