Intravenous nicardipine does not alter hepatic blood flow after orthotopic liver transplant

Raucoules‐Aimé, M.; Drici, Milou‐Daniel; Goubaux, B.; Labib, Youssef; Ichai, Carole; Gugenheim, Jean; Grimaud, D.

doi:10.1007/bf01712158

Cited by 1 publication

(1 citation statement)

References 16 publications

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“…This finding has been reported in renal impairment studies with lidocaine, nicardipine, propranolol, and sildenafil [15][16][17][18]. An initial hypothesis was that, for drugs that are primarily cleared through metabolism, those with a high hepatic extraction ratio are more likely to demonstrate a substantial decrease in clearance with renal impairment; lidocaine, nicardipine, propranolol, and sildenafil are all drugs with intermediate to high hepatic extraction ratios [19][20][21][22]. However, lorlatinib is a low extraction ratio drug (estimated as 12%) [23].…”

Section: Discussionmentioning

confidence: 55%

A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in Adults with Mild, Moderate, and Severe Renal Impairment

Lin

Gong

Canas

et al. 2022

Eur J Drug Metab Pharmacokinet

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Background and Objectives Lorlatinib is approved (100 mg once daily [QD]) for the treatment of patients with anaplastic lymphoma kinase-(ALK) positive metastatic non-small cell lung cancer. This study evaluated the impact of varying degrees of renal impairment on the safety and pharmacokinetics of lorlatinib. Methods Participants were assigned to mild, moderate, and severe renal impairment groups and to a matching normal renal function group based on absolute estimated glomerular filtration rate (eGFR, based on the Modification of Diet in Renal Disease equation and adjusted for body surface area [BSA]) and were evaluated for pharmacokinetics and safety. Results A total of 29 participants (5 with severe renal impairment; 8 each with moderate and mild impairment and normal renal function) were enrolled and received a single dose of lorlatinib 100 mg. One of the participants with severe renal impairment had end-stage renal disease with a baseline absolute eGFR of 10.3 mL/min. No serious adverse events (AEs) were reported. Eighteen AEs, all mild or moderate in severity, were reported by 12 participants (5, 2, 4, and 1 in the normal, mild, moderate, and severe groups, respectively). Area under the plasma concentration-time profile from time zero extrapolated to infinity (AUC inf ) for lorlatinib was increased by 4%, 19%, and 41% in the mild, moderate, and severe renal impairment groups, respectively, compared with the normal renal function cohort. Conclusion Lorlatinib 100 mg was well tolerated. As participants with mild and moderate renal impairment did not experience clinically meaningful increases in lorlatinib exposure, no lorlatinib dose adjustment is recommended in these populations. Patients with severe renal impairment are recommended to reduce the starting dose of lorlatinib from 100 mg QD to 75 mg QD. Clinicaltrials.gov identifier NCT03542305 (available May 31, 2018 on clinicaltrials.gov)

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Section: Discussionmentioning

confidence: 55%

A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in Adults with Mild, Moderate, and Severe Renal Impairment

Lin

Gong

Canas

et al. 2022

Eur J Drug Metab Pharmacokinet

View full text Add to dashboard Cite

show abstract

Intravenous nicardipine does not alter hepatic blood flow after orthotopic liver transplant

Abstract: Nicardipine administration after liver transplantation appears to have no deleterious effects on HBF. Nicardipine can be classified as a drug of intermediate hepatic extraction coefficient, whose elimination partly depends on hepatic enzyme activity.

Cited by 1 publication

References 16 publications

A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in Adults with Mild, Moderate, and Severe Renal Impairment

A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in Adults with Mild, Moderate, and Severe Renal Impairment

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