Determination of Drug Absorption Rates Without Chemical Assay

“…The slope of that line (and therefore the product of concentration and time) is not only a function of the intrinsic potency or toxicity of the drug but also of its absorption rate constant (51, 52). These relationships have been used to determine the absorption rate constants of different barbi turates(52), the relationship between pH and absorption rate of a weak acid(51), and the effect of complex formation on drug absorption(53).Linear relationships between the reciprocal of the time of onset of pharma cologic effect (usually death) in fish and concentration in the bathing , fluid…”

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confidence: 99%

Pharmacokinetics of Drug Action

Lévy¹,

Gibaldi²

1972

Annu. Rev. Pharmacol.

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This is a review of the literature since 1960 on the kinetics of reversible pharmacologic effects in intact animals including man. No claim is made that this is a complete survey. It is practically impossible to conduct an effective literature search on the pharmacokinetics of drug action, since ti tles of papers and index terms do not usually indicate that the investigations are concerned with the time course of pharmacologic effects in relation to dose or drug concentrations. The kinetics of drug absorption, distribution, and elimination are not included in this review. The literature in this field has been reviewed only recently (1) and this subject has been dealt with in a number of recently published books (2-4). This review will consist of four sections. These will summarize the literature on the relationship be tween drug concentration and pharmacologic effect, the kinetics of drug ac tion in cases where the body can be characterized as a single compartment, the kinetics of drug action when the body acts as a multi-compartment sys tem, and the kinetics of indirect pharmacologic effects. While there has been some theoretical work on these subjects before 1960, most of the ex perimental studies and the quantitative correlations between the time course of drug levels in the body and the time course of pharmacologic effects have been carried out since then. These investigations were made possible largely by the extensive progress in analytical and computational methodology as well as in the ability to quantitate certain pharmacologic effects in animals and man. DRUG CONCENTRATION AND PHARMACOLOGIC EFFECTThe concept of a direct and rapidly reversible pharmacologic effect im plies that a given intensity of effect is associated with a particular drug concentration at the site of action. Consequently, there is likely to be a cor responding relationship between the intensity of a pharmacologic effect and the post-distributive concentration of drug in plasma or serum. For exam ple, in studies of individual differences in the effect of drugs in relation to drug concentration in tissues of rats, it has been found that the duration of narcosis produced by a constant dose of pentobarbital sodium differed widely in different rats. However the concentrations of pentobarbital in the brain and serum of these rats upon awakening showed no such differences 85 6529 Annu. Rev. Pharmacol. 1972.12:85-98. Downloaded from www.annualreviews.org Access provided by University of Sussex on 08/19/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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“…The utility of fish for the study of drugs is enhanced further by the fact that they are subject to many diseases similar to those of man (1 1 of biologic membranes to certain drugs, and for determinations of the effect of environmental factors, such as pH and complex formation, on drug absorption (12, 13). These investigations also have resulted in the development of a method for the determination of drug absorption rates without chemical assay (14). There remained, however, a number of unresolved questions with respecL to the transfer of drugs and other foreign substances across fish membranes: What are the relative rates of absorption and exsorptionl of a given substance under similar conditions?…”

mentioning

confidence: 99%