Triazolam liver

MgCl2 (10 mM) increased the apparent Km (83 to 173 /am) and reduced the Vjnax (3.4 to 2.4 min-1) of triazolam 4-hydroxylation by expressed CYP3A4 [21]. However, both MgCl2 (30 mM) and CaCl2 (30 mM) significantly increased reaction rates of testosterone 6/3-hydroxylation (approximately threefold) and nifedipine oxidation (three- to six-fold) by human liver microsomes (HLMs) or recombinant CYP3A4 (reconstituted with b5 and GSH) [15]. It was suggested that divalent cation stimulation on the activity was related to involvement of b5 in CYP 3A4 reaction. 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

Benzodiazepines are lipid soluble and are found in breast milk. They are metabolized in the liver and excreted as glucuro-nide metabolites at different rates. For example, the half-life of triazolam is 2 to 5 hours, while that of diazepam varies between... 

Kronbach T, Mathys D, Umeno M, Gonzalez EJ, Meyer UA. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol Pharmacol 1989 36(l) 89-96. 

Figure 3 Rates of formation of 4-OH-triazolam from triazolam (250 pM) by human liver microsomes in vitro. Each point is the mean ( SE) of four microsomal preparations. Reaction velocities when preparations were preincubated with the macrolide agents are expressed as a percentage of the control velocity with no inhibitor present (inhibitor = 0). Mean IC50 were TAO, 3.3 pM erythromycin, 27.3 pM clarithromycin, 25.2 pM azithromycin, >250 pM. Abbreviations IC50, 50% inhibitory concentrations TAO, troleandomycin. Source Adapted, in part, from Ref. 77.

Kanamitsu S, Ito K, Green CE, Tyson CA, Shimada N, Sugiyama Y. 2000a. Prediction of in vivo interaction between triazolam and erythromycin based on in vitro studies using human liver microsomes and recombinant human CYP3A4. Pharm Res 17 419 426. 

A 77-year-old woman was found dead in her bathtub. She had a history of depression, liver disease, spinal stenosis, and diabetes mellitus. An empty bottle of triazolam was found in the bin. At autopsy there was no injury or evidence of drowning. There was triazolam 0.12 mg/1 in the heart blood. 

Restoril) Triazolam (Halcion) liver, and excreted in urine ... 

Patki, K.C., von Moltke, L.L. and Greenblatt, D.J. (2003) In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes P-450 role of CYP3A4 and CYP3A5. Drug Metabolism and Disposition The Biological Fate of Chemicals, 31, 938-944. 

With the exception of temazepam, which is eliminated by conjugation, all benzodiazepine hypnotics are metabolized by hepatic microsomal oxidation and then undergo glucuronide conjugation. Oxidation may be inhibited in patients with impaired liver function, advanced age, or concurrent use of drugs that inhibit oxidation. Drugs that inhibit the cytochrome P450 3A4 enzyme (e.g., erythromycin, nefazodone, fluvoxamine, and ketoconazole) reduce the clearance of triazolam and increase its plasma concentrations."... 

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