Assessment of body mass-related covariates for rifampicin pharmacokinetics in healthy Caucasian volunteers.
Purpose: Currently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin's pharmacokinetics (PK) parameters in more de...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 80; no. 9; pp. 1271 - 1284 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Sep2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=178855709&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 178855709 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Sep2024 vid: 80 iid: 9 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 178855709 177123744 178855709 178855709 10.1007/s00228-024-03697-3 178855709 ppf: 1271 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Assessment of body mass-related covariates for rifampicin pharmacokinetics in healthy Caucasian volunteers. aug: au: Bilal, Muhammad Ullah, Sami Jaehde, Ulrich Trueck, Christina Zaremba, Dario Wachall, Bertil Wargenau, Manfred Scheidel, Bernhard Wiesen, Martin H. J. Gazzaz, Malaz Chen, Chunli Büsker, Sören Fuhr, Uwe Taubert, Max Dokos, Charalambos affil: Department I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany sug: subj: Rifampin Pharmacokinetics Rifampin Administration and Dosage White Persons Volunteer Workers Body Composition Body Size Human Male Female Sex Factors Body Weight Body Height Descriptive Statistics Germany Body Mass Index Adolescence Adult Middle Age Aged Aged, 80 and Over Body Surface Area Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Male Female ab: Purpose: Currently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin's pharmacokinetics (PK) parameters in more detail using non-linear mixed effects modeling (NLMEM). Methods: Twenty-four healthy Caucasian volunteers were enrolled in a bioequivalence study, each receiving a test and a reference tablet of 600 mg of rifampicin separated by a wash-out period of at least 9 days. Monolix version 2023R1 was used for NLMEM. Monte Carlo simulations (MCS) were performed to visualize the relationship of body size descriptors to the exposure to rifampicin. Results: A one-compartment model with nonlinear (Michaelis–Menten) elimination and zero-order absorption kinetics with a lag time best described the data. The covariate model including fat-free mass (FFM) on volume of distribution (V/F) and on maximum elimination rate (Vmax/F) lowered the objective function value (OFV) by 56.4. The second-best covariate model of sex on V/F and Vmax/F and BW on V/F reduced the OFV by 51.2. The decrease in unexplained inter-individual variability on Vmax/F in both covariate models was similar. For a given dose, MCS showed lower exposure to rifampicin with higher FFM and accordingly in males compared to females with the same BW and body height. Conclusion: Our results indicate that beyond BW, body composition as reflected by FFM could also be relevant for optimized dosing of rifampicin. This assumption needs to be studied further in patients treated with rifampicin. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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