Time Course of Drug Effect

Pharmacokinetic (PK)/pharmacodynamic (PD) modeling is a scientific tool to help developers select a rational dosage regimen for confirmatory clinical testing. This article describes some of the limitations associated with traditional dose-titration designs (parallel and crossover designs) for determining an appropriate dosage regimen. It also explains how a PK/PD model integrates the PK model (describing the relationship between dose, systemic drug concentrations, and time) with the PD model (describing the relationship between systemic drug concentration and the effect vs time profile) and a statistical model (particularly, the intra- and interindividual variability of PK and/or PD origin). Of equal importance is the utility of these models for promoting rational drug selection on the basis of effectiveness and selectivity. PK/PD modeling can be executed using various approaches, such as direct versus indirect response models and parametric versus nonparametric models. PK/PD concepts can be applied to individual dose optimization. Examples of the application of PK/PD approaches in veterinary drug development are provided, with particular emphasis given to nonsteroidal anti-inflammatory drugs. The limits of PK/PD approaches include the development of appropriate models, the validity of surrogate endpoints, and the acceptance of these models in a regulatory environment.

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“…Technical aspects of PK/PD modeling have been widely discussed elsewhere. [5][6][7][8][9][10][11][12][13]…”

Section: Pharmacokinetic/pharmacodynamic Integration In Drug Developmmentioning

confidence: 99%

“…When drug effect corresponds to the inhibition of a biological process, the drug effect is subtracted from the baseline (E 0 ) and Equation 8 can be rewritten: (9) where IC 50 is the concentration producing 50% of the maximum inhibition effect (Emax).…”

Section: Dose-effect Relationship and The Limits Thereofmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic integration in drug development and dosage-regimen optimization for veterinary medicine

Toutain

2002

AAPS J

107

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“…They must be prescribed or purchased by informed or trained person, be appropriate for the complaints and be taken in the right dosage regimen at the right time. 15 In the present study, mothers and patent medicine dealers together accounted for majority (67.4%) of the "prescriptions" for home treatment. This observation is worrisome in that it UHÀHFWV WKH JUHDW GDQJHU WKHVH FKLOGUHQ DUH H[SRVHG WR IURP inappropriate treatment and possible drug toxicities from over-dosage, since both the mother and the patent medicine dealers are not trained to appreciate the contraindications and side-effects of the drugs they administer.…”

Section: Discussionmentioning

confidence: 56%

Common childhood symptoms and rural home-treatment practices

Onyiriuka¹,

Francisca²

2013

Journal of Institute of Medicine

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Introduction: At home, mothers are usually the first to identify symptoms in their children and initiate treatment but there is paucity of information on these initial steps taken by these mothers. The objective of the study is to examine how mothers treat common childhood symptoms at home before presentation in the hospital. Methods: A hospital-based cross-sectional study along with a structured interviewer- administered questionnaire was used for data collection from 307 consecutive mothers. Data obtained included their children’s presenting symptoms, drugs administered, dosage regimen, source of the drugs, person who prescribed the drugs and storage of drugs. The axillary temperature of all the children were measured, using a mercury thermometer with the arm held firmly to the body. Results: Fever either alone or in association with other symptoms was the commonest (75.6%) presenting symptom. Among the 232 children reported as feverish by their mothers, 119 (51.3%) had normal body temperature (<37.50C) while the remaining 113 (48.7%) had elevated axillary temperature equal or greater than 37.50C. Analgesics, antimalarials and antibiotics were the three leading classes of drugs administered by the mothers, together accounting for 62.3% of all drugs. Antimalarials was the class of drug whose dosage regimen was most frequently incorrect, being correct in only 21.4% of cases. Mothers and patent medicine dealers accounted for 67.4% of all the prescriptions. The principal source of drugs was the patent medicine stores (62.2%). Of the 307 mothers, 64 (20.8%) administered left over drugs prescribed for a previous ailment. These drugs were stored mostly in closed cupboards and drawers (67.2% of cases) for a period of three to eight weeks (mean 5.2+0.8 weeks). The mothers had difficulty in correctly identifying fever with 51.3% of cases reported as feverish by their mothers having normal axillary temperature. Conclusions: The present home-treatment practices by mothers regarding their children’s symptoms is greatly deficient. Intervention aimed at improving the situation should include teaching mothers how to give oral drugs correctly, treat local infections, feed and give fluids during illnesses as well as ways of recognizing signs indicating immediate return to the health facility. Training of patent medicine dealers on the basics of drug action is also essential. DOI: http://dx.doi.org/10.2126/joim.v35i1.8893 Journal of Institute of Medicine, April, 2013; 35:23-27

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“…The conditions of the challenge must be well standardized not only within a study but also across studies so that the results are comparable. 15 It is important to keep in mind that to fully understand the PK/PD relationship, it may be necessary to invoke a pharmacodynamic model that allows for interaction between multiple active moieties (i.e., endogenous compound or challenge compound). In some cases, the pharmacokinetics and pharmacodynamics of a challenge compound may be as relevant as that of the primary compound of interest.…”

Section: Challenge Responsementioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Modeling in Drug Research and Development

Derendorf

Lesko

Chaikin³

et al. 2000

The Journal of Clinical Pharma

164

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The two domains in clinical pharmacology dealing with optimizing dosing recommendations are pharmacokinetics and pharmacodynamics. However, the usefulness of these disciplines is limited if viewed in isolation. Pharmacokinetic/pharmacodynamic (PK/PD) relationships and modeling builds the bridge between these two classical disciplines of clinical pharmacology. It links the concentration‐time profile as assessed by pharmacokinetics to the intensity of observed response as quantified by pharmacodynamics. Thus, the resulting so‐called integrated PK/PD‐models allow the description of the complete time course of the desired and/or undesired effects in response to a drug therapy. PK/PD‐modeling can elucidate the causative relationship between drug exposure and response and provide a better understanding of the sequence of events that result in the observed drug effect. This information can then be used to streamline the drug development process and dose optimization. This consensus paper presents an update on the current state of PK/PD‐modeling from an academic, industrial and regulatory perspective.

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Time Course of Drug Effect

Cited by 6 publications

References 39 publications

Pharmacokinetic/pharmacodynamic integration in drug development and dosage-regimen optimization for veterinary medicine

Pharmacokinetic/pharmacodynamic integration in drug development and dosage-regimen optimization for veterinary medicine

Common childhood symptoms and rural home-treatment practices

Pharmacokinetic/Pharmacodynamic Modeling in Drug Research and Development

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