当前位置： SCI文献检索 > LIFE SCIENCES期刊下所有文献 > Recent advances in chronopharmacokinetics: methodological problems.

Recent advances in chronopharmacokinetics: methodological problems.

Abstract：

:Chronopharmacokinetics deals with the study of the temporal changes in absorption, distribution, metabolism and elimination and thus takes into account the influence of time of administration on these different steps. In the last decade, numerous studies have been devoted to chronokinetics: recent advances will be reviewed in the first part. As representative examples, the main chronokinetic changes of anaesthetics, cardiovascular active drugs and antiinflammatory drugs in men are listed. Temporal changes can be involved at each step of the sequence of pharmacokinetic processes: temporal variations in drug absorption from the gastro-intestinal tract, in plasma protein binding and drug distribution, in drug metabolism (temporal variations in enzyme activity, hepatic blood flow) and in renal drug excretion may play a role. Thus, the time of administration of a drug is an important source of variation which must be taken into account in kinetic studies and particular methodological aspects of chronokinetics are needed. In a chronopharmacokinetic study many factors of variation must be controlled: factors related to the drug itself (influence of food, galenic formulation, drug interactions), subject related-factors (age, gender, pathology, posture, exercise, synchronization) and factors related to the conditions of the administration (single or repeated dosing, constant rate delivery, route of administration). In conclusion, there are some instances in which a chronokinetic study is needed: 1) when possible daily variations in pharmacokinetics may be responsible for time dependent variations in drug effects, 2) when drugs have a narrow therapeutic range, 3) when symptoms of a disease are clearly circadian phase-dependent (e.g. nocturnal asthma, angina pectoris, myocardial infarction, ulcer disease) 4) when drug plasma concentrations are well correlated to the therapeutic effect in case the latter is circadian phase-dependent. Variables influencing pharmacokinetics such as fasting, meals and meal times, galenic formulation, posture, activity-rest, have to be controlled according to the aim of the investigation. The main aim of chronokinetic studies is to control the time of administration which among others, can be responsible for variations of drug kinetics but also may explain chronopharmacological effects observed with certain drugs.

journal_name

Life Sci

journal_title

Life sciences

authors

Bruguerolle B,Lemmer B

doi

10.1016/0024-3205(93)90001-j

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

1809-24

issue

eissn

0024-3205

issn

1879-0631

pii

0024-3205(93)90001-J

journal_volume

pub_type

杂志文章,评审

在线工具

Recent advances in chronopharmacokinetics: methodological problems.