Estimation of the minimum permeability coefficient in rats for perfusion-limited tissue distribution in whole-body physiologically-based pharmacokinetics

Jeong, Yoo-Seong; Yim, Chang-Soon; Ryu, Heon-Min; Noh, Chi-Kyoung; Song, YoungGoo; Chung, Suk‐Jae

doi:10.1016/j.ejpb.2017.01.026

Cited by 20 publications

(23 citation statements)

References 84 publications

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“…For PA and NAPA, the PBPK model consisted of eleven major tissues (i.e., adipose, bone, brain, gut, heart, kidney, liver, lung, muscle, skin, and spleen), which were assumed to be connected to the circulatory system (i.e., arterial and venous blood compartments). In the PBPK calculation, the rate of PA and NAPA distribution to tissues was assumed to be perfusion-rate limited and the corresponding standard mass balance differential equations were used [44,48] (see Appendix A).…”

Section: Methodsmentioning

confidence: 99%

“…In this study, passive diffusional clearance of PA, essentially a permeability-surface area product of PA from kidney tissue (i.e., proximal tubule cells) to renal blood compartment (PSout), was obtained by multiplying PAMPA (i.e., parallel artificial membrane permeability assay) permeability (0.310 × 10 −6 cm/s) [54] by the effective surface area values (Seff) for proximal tubule cells, as described previously [44]. On the basis of the similar physicochemical properties of PA and NAPA (Table 2), we assumed PAMPA permeability of NAPA was assumed the same as that of PA.…”

Section: Methodsmentioning

confidence: 99%

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Physiologically-Based Pharmacokinetic Modeling for Drug-Drug Interactions of Procainamide and N-Acetylprocainamide with Cimetidine, an Inhibitor of rOCT2 and rMATE1, in Rats

et al. 2019

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Previous observations demonstrated that cimetidine decreased the clearance of procainamide (PA) and/or N-acetylprocainamide (NAPA; the primary metabolite of PA) resulting in the increased systemic exposure and the decrease of urinary excretion. Despite an abundance of in vitro and in vivo data regarding pharmacokinetic interactions between PA/NAPA and cimetidine, however, a mechanistic approach to elucidate these interactions has not been reported yet. The primary objective of this study was to construct a physiological model that describes pharmacokinetic interactions between PA/NAPA and cimetidine, an inhibitor of rat organic cation transporter 2 (rOCT2) and rat multidrug and toxin extrusion proteins (rMATE1), by performing extensive in vivo and in vitro pharmacokinetic studies for PA and NAPA performed in the absence or presence of cimetidine in rats. When a single intravenous injection of PA HCl (10 mg/kg) was administered to rats, co-administration of cimetidine (100 mg/kg) significantly increased systemic exposure and decreased the systemic (CL) and renal (CLR) clearance of PA, and reduced its tissue distribution. Similarly, cimetidine significantly decreased the CLR of NAPA formed by the metabolism of PA and increased the AUC of NAPA. Considering that these drugs could share similar renal secretory pathways (e.g., via rOCT2 and rMATE1), a physiologically-based pharmacokinetic (PBPK) model incorporating semi-mechanistic kidney compartments was devised to predict drug-drug interactions (DDIs). Using our proposed PBPK model, DDIs between PA/NAPA and cimetidine were successfully predicted for the plasma concentrations and urinary excretion profiles of PA and NAPA observed in rats. Moreover, sensitivity analyses of the pharmacokinetics of PA and NAPA showed the inhibitory effects of cimetidine via rMATE1 were probably important for the renal elimination of PA and NAPA in rats. The proposed PBPK model may be useful for understanding the mechanisms of interactions between PA/NAPA and cimetidine in vivo.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Physiologically-Based Pharmacokinetic Modeling for Drug-Drug Interactions of Procainamide and N-Acetylprocainamide with Cimetidine, an Inhibitor of rOCT2 and rMATE1, in Rats

et al. 2019

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“…Bidirectional transport studies were carried out as described previously (Jeong et al, 2017). Briefly, MDCKII cells were seeded on Transwell filters (12 mm diameter, 0.4 mm pore size; Corning, Corning, NY) at a density of 0.5 Â 10 6 cells/ml and then cultured for 5 to 6 days before being used in transport assays.…”

Section: Methodsmentioning

confidence: 99%

Suppression of Canine ATP Binding Cassette ABCB1 in Madin-Darby Canine Kidney Type II Cells Unmasks Human ABCG2-Mediated Efflux of Olaparib

Song

Park

et al. 2018

J Pharmacol Exp Ther

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Endogenous canine ATP binding cassette B1 (cABCB1) is expressed abundantly in Madin-Darby canine kidney type II (MDCKII) cells, and its presence often complicates phenotyping of the transport process. Errors in estimating the corrected efflux ratio (cER), as a result of the variable expression of cABCB1, were examined for the dual substrates of ABCB1 and ABCG2 in MDCKII cells expressing human ABCG2 (hABCG2). cABCB1 mRNA and protein expression was 60% and 55% lower, respectively, in MDCKII cells expressing hABCG2 compared with the wild type, suggesting that the expression of endogenous cABCB1 became variable after the expression of hABCG2. To minimize the contribution of endogenous efflux, cABCB1 was suppressed kinetically (using verapamil as a selective inhibitor) or biochemically (transfecting short-hairpin RNA against cABCB1). Under these suppression conditions, cER values for irinotecan and topotecan (dual substrates of ABCB1 and ABCG2) were elevated by more than 4-fold and 2-fold, respectively, compared with cER values without the suppression. The cER of olaparib was similarly increased to 3-and 5-fold in MDCKII cells under the kinetic and biochemical suppression of cABCB1, respectively, suggesting that hABCG2-mediated efflux cannot be ruled out for olaparib. Since the substrate selectivity for ABCB1 and ABCG2 overlapped considerably, the possibility of an inaccurate estimation of cER must be considered for dual substrates in the case of the variable expression of cABCB1 in MDCKII cells.

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“…When necessary, the accumulation of MPP+ in MDCK cells (i.e. uptake) was determined using a previously described method, with minor modifications . Briefly, MDCK‐hOCT2, MDCK‐rOCT2 and MDCK‐mock cells were grown in Dulbecco's modified Eagle's medium with 10% (v/v) fetal bovine serum, a 1% (v/v) non‐essential amino acid solution, 100 units/ml penicillin/streptomycin and 10 m m HEPES.…”

Section: Methodsmentioning

confidence: 99%

“…uptake) was determined using a previously described method, with minor modifications. [27][28][29] Briefly, MDCK-hOCT2, MDCK-rOCT2 and MDCK-mock cells were grown in Dulbecco's modified Eagle's medium with 10% (v/v) fetal bovine serum, a 1% (v/v) non-essential amino acid solution, 100 units/ml penicillin/streptomycin and 10 mM HEPES. All cells were kept at 37°C with 5% CO 2 and 95% relative humidity.…”

Section: Uptake Of Mpp+ In Oct2 Expressing Mdck Cellsmentioning

confidence: 99%

The conditional stimulation of rat organic cation transporter 2, but not its human ortholog, by mesoridazine: the possibility of the involvement of the high-affinity binding site of the transporter in the stimulation

Hyung

Pyeon

Park

et al. 2017

Journal of Pharmacy and Pharmacology

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Estimation of the minimum permeability coefficient in rats for perfusion-limited tissue distribution in whole-body physiologically-based pharmacokinetics

Cited by 20 publications

References 84 publications

Physiologically-Based Pharmacokinetic Modeling for Drug-Drug Interactions of Procainamide and N-Acetylprocainamide with Cimetidine, an Inhibitor of rOCT2 and rMATE1, in Rats

Physiologically-Based Pharmacokinetic Modeling for Drug-Drug Interactions of Procainamide and N-Acetylprocainamide with Cimetidine, an Inhibitor of rOCT2 and rMATE1, in Rats

Suppression of Canine ATP Binding Cassette ABCB1 in Madin-Darby Canine Kidney Type II Cells Unmasks Human ABCG2-Mediated Efflux of Olaparib

The conditional stimulation of rat organic cation transporter 2, but not its human ortholog, by mesoridazine: the possibility of the involvement of the high-affinity binding site of the transporter in the stimulation

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