Dataset Information

Population pharmacokinetic analysis of doripenem for Japanese patients in intensive care unit.

ABSTRACT: We aimed to construct a novel population pharmacokinetics (PPK) model of doripenem (DRPM) for Japanese patients in intensive care unit, incorporating the clearance of DRPM by continuous renal replacement therapy (CRRT). Twenty-one patients treated with DRPM (0.25 or 0.5 g) by intravenous infusion over 1 h were included in the study. Nine of the 21 patients were receiving CRRT. Plasma samples were obtained before and 1, 2, 4, 6 and 8 h after the first DRPM administration. PPK analysis was conducted by nonlinear mixed effects modeling using a two-compartment model. Total clearance (CL_total) in the model was divided into CRRT clearance (CL_CRRT) and body clearance (CL_body). The final model was: CL_total (L h^-1) = CL_{body(non-CRRT)} = 3.65 × (Ccr/62.25)^0.64 in the absence of CRRT, or = CL_body(CRRT) + CL_CRRT = 2.49 × (Ccr/52.75)^0.42 + CL_CRRT in the presence of CRRT; CL_CRRT = Q_E × 0.919 (0.919 represents non-protein binding rate of DRPM); V₁ (L) = 10.04; V₂ (L) = 8.13; and Q (L h^-1) = 3.53. Using this model, CL_total was lower and the distribution volumes (V₁ and V₂) tended to be higher compared to previous reports. Also, Ccr was selected as a significant covariate for CL_body. Furthermore, the contribution rate of CL_CRRT to CL_total was 30-40%, suggesting the importance of drug removal by CRRT. The population analysis model used in this study is a useful tool for planning DRPM regimen and administration. Our novel model may contribute greatly to proper use of DRPM in patients requiring intensive care.

SUBMITTER: Nonoshita K

PROVIDER: S-EPMC7747597 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Population pharmacokinetic analysis of doripenem for Japanese patients in intensive care unit.

Nonoshita Ko K Suzuki Yosuke Y Tanaka Ryota R Kaneko Tetsuya T Ohchi Yoshifumi Y Sato Yuhki Y Yasuda Norihisa N Goto Koji K Kitano Takaaki T Itoh Hiroki H

Scientific reports 20201217 1

We aimed to construct a novel population pharmacokinetics (PPK) model of doripenem (DRPM) for Japanese patients in intensive care unit, incorporating the clearance of DRPM by continuous renal replacement therapy (CRRT). Twenty-one patients treated with DRPM (0.25 or 0.5 g) by intravenous infusion over 1 h were included in the study. Nine of the 21 patients were receiving CRRT. Plasma samples were obtained before and 1, 2, 4, 6 and 8 h after the first DRPM administration. PPK analysis was conduct ...[more]

PMID: 33335198

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Dataset Information

Population pharmacokinetic analysis of doripenem for Japanese patients in intensive care unit.

Publications

Population pharmacokinetic analysis of doripenem for Japanese patients in intensive care unit.

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