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Population pharmacokinetics of tazobactam/ceftolozane in Japanese patients with complicated urinary tract infection and complicated intra-abdominal infection.
J Infect Chemother. 2019 Mar; 25(3):182-191.JI

Abstract

Tazobactam/ceftolozane is a combination of a β-lactamase inhibitor and a cephalosporin antibiotic, with recommended dosage for patients with normal renal function of tazobactam 0.5 g/ceftolozane 1 g administered as a 1-h intravenous infusion every 8 h. The doses in patients with moderate and severe renal impairment are recommended to be reduced by half and 1/4th, respectively. The dose in patients undergoing dialysis is a single loading dose of 750 mg followed after 8 h by a 150 mg maintenance dose. In order to evaluate pharmacokinetics (PK) in Japanese patients, individual Bayes PK parameters were derived using the previously developed population PK models. Furthermore, attainment of PK/pharmacodynamic target in Japanese patients was calculated to confirm the recommended dosage. Based on PK data from 200 Japanese patients in the phase 3 studies, including patients with mild and moderate renal impairment, individual tazobactam/ceftolozane PK parameters were derived. No clinically relevant difference was observed in tazobactam/ceftolozane exposures between Japanese and non-Japanese patients. All Japanese patients achieved a target percent of time that free ceftolozane concentrations are above the minimum inhibitory concentration (MIC) of 30% for MICs of up to 8 μg/mL. Also for tazobactam, all Japanese patients achieved a target percent of time that the free tazobactam concentration exceeds a threshold concentration (1 μg/mL) of 20%. The results suggest that the doses will be efficacious in the Japanese population. The results indicate that the recommended dose in patients with normal renal function or renal impairment is appropriate in Japanese patients.

Authors+Show Affiliations

Clinical Pharmacokinetics & Pharmacometrics Group, Clinical Pharmacology Development, Clinical Research Area, Japan Development, MSD K.K., Tokyo, Japan. Electronic address: makoto.kakara@merck.com.Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Inc., Kenilworth, NJ, USA.Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Inc., Kenilworth, NJ, USA.Clinical Pharmacokinetics & Pharmacometrics Group, Clinical Pharmacology Development, Clinical Research Area, Japan Development, MSD K.K., Tokyo, Japan.Clinical Pharmacokinetics & Pharmacometrics Group, Clinical Pharmacology Development, Clinical Research Area, Japan Development, MSD K.K., Tokyo, Japan.Department of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Inc., Kenilworth, NJ, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study

Language

eng

PubMed ID

30528208

Citation

Kakara, Makoto, et al. "Population Pharmacokinetics of Tazobactam/ceftolozane in Japanese Patients With Complicated Urinary Tract Infection and Complicated Intra-abdominal Infection." Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy, vol. 25, no. 3, 2019, pp. 182-191.
Kakara M, Larson K, Feng HP, et al. Population pharmacokinetics of tazobactam/ceftolozane in Japanese patients with complicated urinary tract infection and complicated intra-abdominal infection. J Infect Chemother. 2019;25(3):182-191.
Kakara, M., Larson, K., Feng, H. P., Shiomi, M., Yoshitsugu, H., & Rizk, M. L. (2019). Population pharmacokinetics of tazobactam/ceftolozane in Japanese patients with complicated urinary tract infection and complicated intra-abdominal infection. Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy, 25(3), 182-191. https://doi.org/10.1016/j.jiac.2018.11.005
Kakara M, et al. Population Pharmacokinetics of Tazobactam/ceftolozane in Japanese Patients With Complicated Urinary Tract Infection and Complicated Intra-abdominal Infection. J Infect Chemother. 2019;25(3):182-191. PubMed PMID: 30528208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Population pharmacokinetics of tazobactam/ceftolozane in Japanese patients with complicated urinary tract infection and complicated intra-abdominal infection. AU - Kakara,Makoto, AU - Larson,Kajal, AU - Feng,Hwa-Ping, AU - Shiomi,Mari, AU - Yoshitsugu,Hiroyuki, AU - Rizk,Matthew L, Y1 - 2018/12/04/ PY - 2018/08/25/received PY - 2018/11/02/revised PY - 2018/11/07/accepted PY - 2018/12/12/pubmed PY - 2019/4/4/medline PY - 2018/12/12/entrez KW - Ceftolozane KW - Complicated intra-abdominal infection (cIAI) KW - Complicated urinary tract infection (cUTI) KW - Empirical Bayes estimate analysis KW - Japanese patients KW - Population pharmacokinetics SP - 182 EP - 191 JF - Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy JO - J Infect Chemother VL - 25 IS - 3 N2 - Tazobactam/ceftolozane is a combination of a β-lactamase inhibitor and a cephalosporin antibiotic, with recommended dosage for patients with normal renal function of tazobactam 0.5 g/ceftolozane 1 g administered as a 1-h intravenous infusion every 8 h. The doses in patients with moderate and severe renal impairment are recommended to be reduced by half and 1/4th, respectively. The dose in patients undergoing dialysis is a single loading dose of 750 mg followed after 8 h by a 150 mg maintenance dose. In order to evaluate pharmacokinetics (PK) in Japanese patients, individual Bayes PK parameters were derived using the previously developed population PK models. Furthermore, attainment of PK/pharmacodynamic target in Japanese patients was calculated to confirm the recommended dosage. Based on PK data from 200 Japanese patients in the phase 3 studies, including patients with mild and moderate renal impairment, individual tazobactam/ceftolozane PK parameters were derived. No clinically relevant difference was observed in tazobactam/ceftolozane exposures between Japanese and non-Japanese patients. All Japanese patients achieved a target percent of time that free ceftolozane concentrations are above the minimum inhibitory concentration (MIC) of 30% for MICs of up to 8 μg/mL. Also for tazobactam, all Japanese patients achieved a target percent of time that the free tazobactam concentration exceeds a threshold concentration (1 μg/mL) of 20%. The results suggest that the doses will be efficacious in the Japanese population. The results indicate that the recommended dose in patients with normal renal function or renal impairment is appropriate in Japanese patients. SN - 1437-7780 UR - https://www.unboundmedicine.com/medline/citation/30528208/Population_pharmacokinetics_of_tazobactam/ceftolozane_in_Japanese_patients_with_complicated_urinary_tract_infection_and_complicated_intra_abdominal_infection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1341-321X(18)30457-4 DB - PRIME DP - Unbound Medicine ER -