Disposition and clinical pharmacokinetics of theophylline after administration of a new sustained release tablet

Jonkman, Jhg; Berg, Wilhelm; Devries, K; Dezeeuw, Ra; Schoenmaker, R.; Grimberg, N

doi:10.1007/bf00609586

Cited by 13 publications

(4 citation statements)

References 7 publications

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“…& The peak occupancy time (POT) or plateau time is the time span during which the concentration is at some, clinically specified level (e.g., 25% or 50%) below C max thereby yielding the metrics T75%C max and T50%C max (33). T50%C max has also been referred to as the half-value duration (HaVD) (34).…”

Section: Metrics Related To Time In Single-dose Studiesmentioning

confidence: 99%

Metrics for the Evaluation of Bioequivalence of Modified-Release Formulations

Endrényi

Tóthfalusi

2012

AAPS J

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Abstract. Metrics are discussed which are used for the evaluation of bioequivalence of modifiedrelease formulations. In order to ensure the therapeutic equivalence of the compared drug products, it would be important to contrast measures which are additional to area under the curve (AUC) and C max . For delayed-release products, the assessment of lag times is informative. For extended-release dosage forms, comparisons of the half-value duration and the midpoint duration time are useful. For some modified-release formulations with complicated, multiphasic concentration profiles, the comparison of partial AUCs is important. In determinations of the bioequivalence of extended-release dosage forms, investigations performed under steady-state conditions rather than after single dosing can yield enhanced probability of therapeutic equivalence, especially with substantial accumulation of the drug products. In steady-state investigations of bioequivalence, evaluation of the trough concentration and of the peak trough fluctuation is informative.

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Section: Metrics Related To Time In Single-dose Studiesmentioning

confidence: 99%

Metrics for the Evaluation of Bioequivalence of Modified-Release Formulations

Endrényi

Tóthfalusi

2012

AAPS J

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“…In the case of a 50% deviation from the maximum, the plateau time corresponds to the halfvalue duration (HVD) introduced by Meier et al (1974). In the case of controlled-release theophylline formulations, for example, the plateau time refers to the time during which the concentration exceeds 75% of the maximum and, therefore, is denoted by T75%Cmax (Jonkman et al 1981;Steinijans et al 1987). A similar concept led to the 'time above the average concentration at steadystate' as a rate characteristic (Ahr & Schaefer 1991); however, we found that this characteristic has little power to discriminate between formulations.…”

Section: Pharmacokinetic Characteristics Of Rate and Extent Of Absorpmentioning

confidence: 99%

Controversies in Bioequivalence Studies

Steinijans

Hauschke

Jonkman

1992

Clinical Pharmacokinetics

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The design, performance and evaluation of bioequivalence studies have received major attention from academia, the pharmaceutical industry and health authorities over the past decade. Despite the efforts of various regional and national bodies in setting up guidelines and recommendations (APV 1987; CPMP 1991; FDA 1977 FDA , 1988 Nordic Council of Medicines 1987;Skelly 1984), a universal standard is still lacking. Such a standard is becoming ever more necessary, in order to avoid costly and unethical replications of largely identical studies. Although the requests by the various health authorities may appear to differ only marginally, they may lead to different conclusions with regard to approval or rejection of bioequivalence_ Among the issues discussed during a recent workshop of the Drug Information Association (DIA) on 'Bioavailability/Bioequivalence: Pharmacokinetic and Statistical Considerations' (DIA 1991) were the logarithmic transformation of bioequivalence characteristics and the corresponding bioequivalence range. Other controversies concerning the design of bioequivalence studies are: selection of the study population (healthy subjects/ patients, smokers/nonsmokers, normal metabolisers/fast and poor metabolisers); posture (supine/ mobile); fasting or fed conditions and time between drug administration and meal intake; volume of fluid given after drug administration; the selection of the appropriate reference formulation; single vs multiple doses; and the replicated administration of test and reference formulations in the same study participant for 2 periods each. This last would allow investigation of the reproducibility of test and reference formulation, i.e. a comparison of the within-subject variability of test and reference. This has to be seen in connection with the most recent controversy in bioequivalence assessment, namely, whether average bioequivalence is a sufficient criterion to allow interchangeability of generic drugs, or whether the more stringent individual bioequivalence should become a necessary condition (Anderson & Hauck 1990).The option to choose between pharmacokinetic characteristics for rate and extent of absorption has attracted considerable attention from pharmacokineticists, particularly with regard to controlled released formulations (e.g. Steinijans 1990). During the recent DIA workshop it appeared, however, that speakers ofthe US Food and Drug Administration (FDA) still consider area under the plasma concentration-time curve (AUC) and peak concentration (Cmax) as the primary characteristics of extent and rate of absorption, although the limitations of Cmax as a rate characteristic were admitted, and despite other rate characteristics such as the peaktrough fluctuation having been recommended in earlier FDA guidance (Skelly 1984). If pharmacokinetic characteristics cannot be determined, e.g. due to lack of assay sensitivity, pharmacodynamic characteristics may be used; but possible implications for the design of the study (e.g. parallel groups vs crossover) should also b...

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“…In the case of theophylline, for example, Jonkman et a!. (8) originally considered the time interval during which the concentration exceeded 80% of the maximum concentration. Meanwhile, the value of 75% of the maximum concentration is widely accepted and the corresponding plateau time is denoted by T75% C max (9).…”

Section: Characteristics After Single Dosementioning

confidence: 99%

Pharmacokinetic characterization of controlled-release formulations

1990

Eur. J. Drug Metab. Pharmacokinet.

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The development of controlled-release formulations should be based on a clinico-pharmacological rationale such as increased compliance, reduced side effects and improved efficacy. The pharmacokinetic profile of a controlled-release formulation and its dose regimen should be compared under steady-state conditions with that of an immediate-release formulation or that of another controlled-release formulation. Apart from conventional characteristics such as AUC, tmax and Cmax, alternative characteristics are suggested such as residual concentration at the end of the dose interval, peak-through fluctuation in steady state, plateau time, statistical moments, in vivo input functions and intravenous infusion schemes which mimic the concentration/time profile after oral administration of the controlled-release formulation. The pharmacokinetic steady-state profile should be reproduced with and without food, from day to day, and at various dose levels. The in vitro specification should be based on in vivo requirements for "within-product bioequivalence".

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Disposition and clinical pharmacokinetics of theophylline after administration of a new sustained release tablet

Cited by 13 publications

References 7 publications

Metrics for the Evaluation of Bioequivalence of Modified-Release Formulations

Metrics for the Evaluation of Bioequivalence of Modified-Release Formulations

Controversies in Bioequivalence Studies

Pharmacokinetic characterization of controlled-release formulations

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