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Pharmacokinetics of glafenine and glafenic acid in patients with cirrhosis, compared to healthy volunteers
Author(s) -
Vermerie N.,
Kusielewicz D.,
Tod M.,
Nicolas P.,
Perret G.,
Fauvelle F.,
Petitjean O.
Publication year - 1992
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1992.tb00112.x
Subject(s) - pharmacokinetics , cirrhosis , metabolite , medicine , active metabolite , statistical significance , chemistry , regimen , pharmacology , gastroenterology
Summary— Pharmacokinetic parameters were evaluated in 12 patients with alcoholic cirrhosis and 12 healthy volunteers after a single 400 mg oral dose of glafenine. Glafenine (G) and its major active metabolite glafenic acid (GA) were measured at regular intervals using a specific high performance liquid chromatographic method. Glafenine absorption was significantly delayed in cirrhotic patients (CP) (T max = 2.8 ± 1.3 hvs 1.5 ± 0.4 h, p < 0.01) and was dramatically reduced in 3 patients. The large hepatic ‘first pass’ effect observed in healthy volunteers was markedly reduced in CP (ratio C max GA/C max G = 3.6 ± 2.9 vs 18.9 ± 9.8, p < 0.001; ratio areas under the curves AUC GA/AUC G = 2.3 ± 2.3 vs 18.2 ± 11.2, p < 0.001). The elimination half‐life of G was prolonged in the CP (13.0 ± 13.1 h vs 1.5 ± 0.5 h, p < 0.01). In CP, GA elimination half‐life was increased (12.0 ± 13.4 h vs 4.3 ± 1.3 h, NS) but the difference did not reach statistical significance because of large variability. The significant rise of G plasma concentrations ( C max = 2.2 ± 2.1 mg/L vs 0.7 ± 0.2 mg/L, p < 0.05) and its longer half‐life would lead to an accumulation if the usual dosage regimen was prescribed for CP and could result in nephrotoxicity. On the other hand, lower dosage would be ineffective because only GA is active and nephrotoxic. Hence, G should be given with great caution to CP.