IVIVC Revised

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2024 Jan 8

PMID 38191705

Authors

Nikolaos Alimpertis

Antony Simitopoulos

Athanasios A Tsekouras

Panos Macheras

Affiliations

Soon will be listed here.

Abstract

Purpose: To revise the IVIVC considering the physiologically sound Finite Absorption Time (F.A.T.) and Finite Dissolution Time (F.D.T.) concepts.

Methods: The estimates τ and τ for F.A.T. and F.D.T., respectively are constrained by the inequality τ ≤ τ; their relative magnitude is dependent on drug's BCS classification. A modified Levy plot, which includes the time estimates for τ and τ was developed. IVIVC were also considered in the light of τ and τ estimates. The modified Levy plot of theophylline, a class I drug, coupled with the rapid (30 min) and very rapid (15 min) dissolution time limits showed that drug dissolution/absorption of Class I drugs takes place in less than an hour. We reanalyzed a carbamazepine (Tegretol) bioequivalence study using PBFTPK models to reveal its complex absorption kinetics with two or three stages.

Results: The modified Levy plot unveiled the short time span (~ 2 h) of the in vitro dissolution data in comparison with the duration of in vivo dissolution/absorption processes (~ 17 h). Similar results were observed with the modified IVIVC plots. Analysis of another set of carbamazepine data, using PBFTPK models, confirmed a three stages absorption process. Analysis of steady-state (Tegretol) data from a paediatric study using PBFTPK models, revealed a single input stage of duration 3.3 h. The corresponding modified Levy and IVIVC plots were found to be nonlinear.

Conclusions: The consideration of Levy plots and IVIVC in the light of the F.A.T. and F.D.T. concepts allows a better physiological insight of the in vitro and in vivo drug dissolution/absorption processes.

Citing Articles

FDA and EMA Oversight of Disruptive Science on Application of Finite Absorption Time (F.A.T.) Concept in Oral Drug Absorption: Time for Scientific and Regulatory Changes.

Toulitsis E, Tsekouras A, Macheras P Pharmaceutics. 2024; 16(11).

PMID: 39598557 PMC: 11597828. DOI: 10.3390/pharmaceutics16111435.

Application of the Finite Absorption Time (F.A.T.) Concept in the Assessment of Bioequivalence.

Tsekouras A, Macheras P Pharm Res. 2024; 41(7):1413-1425.

PMID: 38898304 DOI: 10.1007/s11095-024-03727-w.

Coupling Drug Dissolution with BCS.

Simitopoulos A, Tsekouras A, Macheras P Pharm Res. 2024; 41(3):481-491.

PMID: 38291164 PMC: 11636680. DOI: 10.1007/s11095-024-03661-x.

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