Effects of Neuroleptic Phenothiazines on the Activities of Aminotransferases and γ-Glutamyltransferase in Serum and Liver

Abstract

Serum alanine aminotransferase, aspartate aminotransferase and -glutamyltransferase activities were monitored in psychiatric patients receiving normal doses of phenothiazine neuroleptics over a 30-day period. The first two enzymes showed slight initial increases and a subsequent return to normal, while the third showed a slight increase. In rats, dosage levels exceeding those used in human therapy produced much larger increases in the catalytic concentrations of all three enzymes in serum (1.4, 0.7 and 0.5 above the control value, respectively), and somewhat smaller increases in the liver homogenates of these animals. Wirkung neuroleptischer Phenothiazine auf die Aktivitäten von Aminotransferasen und y-Glutamyltransferase in Serum und LeberZusammenfassung: In Seren von geisteskranken Patienten wurden die Aktivitäten von Aspartataminotransferase, Alaninaminotransferase und -Glutamyltransferase während einer dreißigtägigen Therapie mit Phenothiazinen bestimmt. Die Änderungen in den Aktivitäten aller drei Enzyme bewegten sich etwa in dem breiteren Grenzbereich der i Referenzwerte.Experimente mit Ratten und größeren Dosen von Arzneimitteln haben signifikante Änderungen in den Enzymaktivitäten gezeigt: die Aktivitäten von Aspartataminotransferase waren bis zu l ,4, von Alaninaminotransferase 0,7 und von -Glutamyltransferase 0,5 mal höher als die Referenzwerte.

Alterations of liver function test in patients treated with antipsychotics

“…Previous reports have suggested an induction of some liver function tests (alkaline phosphatase, GGT) by phenothiazines. This could explain our results of increased alkaline phosphatase values in patients (10,11).…”

Six Months of Treatment with Risperidone May Be Associated with Nonsignificant Abnormalities of Liver Function Tests in Children and Adolescents: A Longitudinal, Observational Study from Turkey

“…Similar results of increased levels of ALP were observed only with other typical antipsychotics, namely phenotiazines, haloperidol, and chlorpromazine, in an adult population (Dincsoy and Saelinger 1982;Obata 1983;Cepelak et al 1986;Hütteroth 1989;Garcia-Unzueta et al 2003). Accordingly, those antipsychotics were reported to induce a cholestatic form of injury or primary liver damage and injury to liver cells caused by cholestasis (Obata 1983;Dölle and Martini 1984;Cepelak et al 1986;Thomas 1995;GarciaUnzueta et al 2003).…”

“…Accordingly, those antipsychotics were reported to induce a cholestatic form of injury or primary liver damage and injury to liver cells caused by cholestasis (Obata 1983;Dölle and Martini 1984;Cepelak et al 1986;Thomas 1995;GarciaUnzueta et al 2003). This elevation of ALP, which is not seen in a risperidone-treated adult population, needs to be carefully evaluated and interpreted (Atasoy et al 2007).…”

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

“…However, DME induction as a direct cause of GGT increases is contradicted by the wide variability in serum GGT activity among human subjects receiving these inducing agents, and lack of correlation between patients' serum GGT activities and DME induction based on urinary excretion of D-glucaric acid or antipyrine clearance (Frezza et al 1989; Heinemeyer et al 1986; Hermida et al 2002; Hildebrandt et al 1975; Ohnhaus and Studer 1983). In addition, weak to no correlation between serum GGT activity and drug dose or plasma drug concentration has been reported in those clinical studies that comparatively evaluated these end points (Aldenhövel 1988; Braide and Davies 1987; Cepelak et al 1986; Sano et al 1981). Collectively, these findings suggest that these increases in serum activity of GGT, as well as other routine hepatobiliary marker enzymes, were not directly related to the DME induction potential of the drugs.…”