A dose reduction by a factor of six is recommended for persons with severe renal failure.

Valsartan, 80 mg, is a potent angiotensin II antagonist with a rapid onset of action and persistent angiotensin II inhibition up to 24 hours. There is no attenuation of this effect after multiple doses.

The concentration of diazepam in the plasma and saliva of 9 normal human subjects receiving a single oral dose of diazepam (10 mg) over an 8-hr The secretion of drugs into saliva has been the subject of many investigations in man. [2][3][4][5][6]11 Both parotid saliva and mixed saliva have been used to evaluate the usefulness of this biologic fluid in predicting blood concentrations of drugs. The exchange of drugs between blood and saliva is determined by many variables, including protein binding, degree of lipid solubility, extent of ionization, and molecular size of the particular drug.Diazepam is a long-acting lipophilic drug, primarily undissociated at physiologic pH, which has a high affinity for plasma proteins,9 The remaining nonprotein bound (free) form of this drug distributes widely throughout the body, particularly into the central nervous system, The free form of diazepam in the central nervous system has been quantitated in human cerebrospinal fluid.9 Little or no information, however, has been published on the availability of the free form (unbound) of diazepam in human salivary secretions.

The pharmacokinetics and bioavailability of nitroglycerin (GTN) and its metabolites, 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN), were compared after a single 14-hour application of Transderm-Nitro (Ciba-Geigy, Summit, NJ), Nitrodisc (GD Searle, Chicago, IL), and Nitro-Dur II (Key Pharmaceuticals, Kenilworth, NJ) systems to 18 healthy male subjects on 3 separate occasions. A 14-hour intravenous infusion of 15N-labeled GTN was given simultaneously to correct for changes in systemic clearance during the application of each system. Plasma concentrations of 15N-labeled GTN, unlabeled GTN, and their corresponding dinitrate metabolites were measured using a gas chromatography/mass spectrometry method. Results showed that the plasma concentration profiles of nitroglycerin and its metabolites for the three systems were similar during and after system removal. Mean (SD) total amounts (AUCp x CLiv) of GTN transdermally available after adjustment for 15N-labeled GTN clearance were 5.3 (2.1), 5.3 (2.0), and 5.4 (2.6) mg for Transderm-Nitro, Nitrodisc, and Nitro-Dur II, respectively. Mean (SD) AUC values for 1,2-GDN were 44.6 (15.8), 44.3 (16.1), and 42.8 (19.3) ng.h/mL for the 3 systems. Corresponding AUC values for 1,3-GDN were 9.3 (2.9), 9.7 (2.9), and 8.7 (3.0) ng.h/mL. Statistical analysis of the log-transformed data based on 90% conventional confidence interval showed that all 3 systems delivered equivalent amounts of nitroglycerin into the systemic circulation. The AUC ratios for 1,3-GDN to GTN, but not 1,2-GDN to GTN, were statistically different for the intravenous and transdermal routes during all 3 system applications, indicating that the formation and metabolism of 1,3-GDN was dependent on route of administration.