Facial Nerve Schwannoma: A Case Report, Radiological Features and Literature Review.

Facial nerve schwannoma localized in the middle fossa is a rare lesion. We report a case of a facial nerve schwannoma in a 30-year-old male presenting with facial nerve palsy. Magnetic resonance imaging (MRI) showed a 3 cm diameter tumor of the right middle fossa.

Pharmacokinetics of maribavir, a novel oral anticytomegalovirus agent, in subjects with varying degrees of renal impairment.

The effect of renal function on the pharmacokinetics of maribavir, a novel anticytomegalovirus agent, was evaluated in 12 adults with normal renal function (creatinine clearance [CrCl] >80 mL/min) and 19 adults with renal impairment classified as mild (n = 5), moderate (n = 5), or severe (n = 9), as measured by CrCl 50-80, 30-49, and <30 mL/min, respectively. After a single oral dose of maribavir 400 mg, the pharmacokinetics of maribavir, based on total and unbound plasma concentrations, showed no statistically significant difference between subjects with normal renal function and subjects with mild/moderate or severe renal impairment. Renal impairment was associated with an increase in area under the plasma concentration-time curve (AUC) values for an inactive metabolite of maribavir, VP 44469.

Inactivation of adrenal cytochromes P450 by 1-aminobenzotriazole. Divergence of in vivo and in vitro actions.

Recent investigations demonstrated that administration of 1-aminobenzotriazole (ABT) to rats caused adrenal gland enlargement. Studies were done to pursue the mechanism(s) involved. Preliminary experiments revealed that the adrenal enlargement caused by ABT was associated with a decline in plasma corticosterone concentrations, suggesting inhibition of adrenal steroidogenesis.

Determination of Ro 23-7637 in dog plasma by multidimensional ion-exchange-reversed-phase high-performance liquid chromatography with ultraviolet detection.

Ro 23-7637 (I) is a new drug under development for the treatment of metabolic diseases. A high-performance liquid chromatographic-ultraviolet detection (HPLC-UV) analytical procedure for its analysis in dog plasma was developed and is reported here. Following C18 solid-phase extraction, the sample is applied to a strong cation-exchange column in the first dimension.

Identification of fenoldopam prodrugs with prolonged renal vasodilator activity.

Fenoldopam (SK&F 82526) is a short-acting selective dopamine-1 agonist in clinical trials for the treatment of hypertension, congestive heart failure and renal failure. In the present study, we tested various N-ethyl carbamate esters of fenoldopam in the conscious dog instrumented with a femoral arterial Vascular-Access-Port and a renal artery flow probe. Oral administration of SK&F R-82526 at 1 and 3 mumol/kg resulted in transient (30-60 min) dose-dependent increases in plasma fenoldopam levels and renal blood flow.

Deuterium isotope effect on the toxicokinetics of monomethylamine in the rat.

The single-dose toxicokinetics of monomethylamine has been characterized in the rat by HPLC assay of serial blood samples. Biphasic first-order elimination was observed following an iv bolus dose of 19 mumol/kg with a terminal half-life of 19.1 +/- 1.

Metabolic denitrosation of N-nitrosodimethylamine in vivo in the rat.

Enzymatic denitrosation is a potentially inactivating metabolic route that has been shown to convert carcinogenic N-nitrosodimethylamine (NDMA) to methylamine (MA) in vitro. To investigate its quantitative course in vivo, groups of 8-week-old male Fischer rats have been given small (8-15 mumol/kg) p.o.

Single-dose toxicokinetics of N-nitrosomethylethylamine and N-nitrosomethyl (2,2,2-trideuterioethyl)amine in the rat.

To investigate the origins of an organotropic shift toward increasing esophageal carcinogenicity and DNA alkylation caused by beta-trideuteration of the hepatocarcinogen, N-nitrosomethylethylamine (NMEA), the single-dose toxicokinetics of NMEA and N-nitrosomethyl(2,2,2-trideuterioethyl)amine (NMEA-d3) has been characterized in 8-week-old male Fischer 344 rats by analysis using high performance liquid chromatography of serial blood samples. An i.v.

Pharmacokinetics and metabolism of SK&F 86002 in male and female Sprague-Dawley rats.

Several pharmacokinetic parameters for SK&F 86002 [6-(4'-fluorophenyl)-5-(4'-pyridyl)-2,3-dihydroimidazo(2,1-b)-thia zole] and its metabolites (sulfoxide, sulfone) were measured in male and female Sprague-Dawley rats after iv (5 mg/kg) and a wide range (10-80 mg/kg) of oral doses of SK&F 86002. In both sexes. SK&F 86002 is metabolized to an active metabolite, sulfone, which has an extended half-life (approximately 13 hr) and, therefore, has the potential to accumulate upon repeated dosing.

Role of pharmacokinetics and metabolism in the enhanced susceptibility of middle-aged male Sprague-Dawley rats to acetaminophen nephrotoxicity.

Middle-aged male Sprague-Dawley (SD) rats (9-12 months) are more susceptible to acetaminophen (APAP)-induced nephrotoxicity than are young (2-3 months) adult males. The present studies were designed to evaluate the role of pharmacokinetics and renal and hepatic metabolism of APAP in age-dependent nephrotoxicity. Following 750 mg/kg APAP, ip, a nephrotoxic dosage in 12-month-old but not 3-month-old rats, renal cortical APAP concentrations were significantly greater in 12-month-old compared with 3-month-old SD rats at 3, 4, and 6 hr after treatment.

Pharmacokinetics of a series of 6-chloro-2,3,4,5-tetrahydro-3-substituted-1H- 3-benzazepines in rats. Determination of quantitative structure-pharmacokinetic relationships.

To aid in the effort to discover novel agents for the treatment of cardiovascular disease, the relationships between pharmacokinetic parameters in the rat and lipophilicity and basicity were studied for a series of 6-chloro-2,3,4,5-tetrahydro-3-substituted-1H-3-benzazepines. Eight compounds, ranging in lipophilicity from log P = 1.64 to 3.

Dose-dependent pharmacokinetics of recombinant tissue-type plasminogen activator in anesthetized dogs following intravenous infusion.

The pharmacokinetics of SK&F recombinant two-chain tissue-type plasminogen activator (tPA) following intravenous (iv) infusion were characterized in anesthetized, open chested mongrel dogs in which artificial intracoronary thrombi were formed. SK&F tPA was infused at rates of 0.5, 1, 2, 4, and 8 micrograms/kg/min (N = 3 to 5 per dose) for 90 min, and arterial blood samples were withdrawn during and after infusion for determination of functionally active tPA concentrations using a modified and validated S-2251 chromogenic assay.

Deuterium isotope effect on denitrosation and demethylation of N-nitrosodimethylamine by rat liver microsomes.

In an attempt to elucidate the molecular basis for the decrease in rat liver carcinogenicity and DNA-alkylating ability that accompanies deuteration of N-nitrosodimethylamine (NDMA), NDMA and its fully deuterated analogue ([2H6]NDMA) were incubated with acetone-induced rat liver microsomes. Rates for the competing metabolic routes, denitrosation and demethylation, were determined from colorimetric data on nitrite and formaldehyde generation, respectively. The Vmax calculated for demethylation of NDMA was 7.

In vivo and in vitro hepatotoxicity and metabolism of acetaminophen in Syrian hamsters.

The purpose of this investigation was to correlate the in vitro and in vivo toxicity of the hepatotoxicant, acetaminophen. Hamsters were pretreated with either phenobarbital (70 mg/kg) or 3-methylcholanthrene (20 mg/kg) or an appropriate vehicle for 3 days. In non-pretreated hamsters, single doses of acetaminophen (200-400 mg/kg i.

Protein binding of glycopeptide antibiotics with diverse physical-chemical properties in mouse, rat, and human serum.

In previous studies of the pharmacokinetics and urinary excretion of nine glycopeptides with diverse isoelectric points (pI), as pI decreases, the total systemic and renal clearance, urinary recovery, and volume of distribution decrease, whereas the half-life increases. With glycopeptides of similar pI, clearance decreases and half-life increases with increasing lipophilicity. The present study examines the serum protein binding of these glycopeptide antibiotics in mouse, rat, and human serum and calculates the previously reported pharmacokinetic parameters for these drugs based on unbound concentration.

Potential for metabolic deactivation of carcinogenic N-nitrosodimethylamine in vivo.

Enzymatic cleavage of N-nitrosodimethylamine (NDMA) to nitrite (normally representing about 10% of the total metabolism in vitro) also produces methylamine in yields roughly equimolar to those of nitrite, suggesting that the 'denitrosation' pathway may be responsible for the previously unexplained detection of methylamine as a urinary metabolite of NDMA and, at least in part, for the recovery of less than stoichiometric amounts of dinitrogen in 15N-labelling experiments. We have now followed excretion of labelled methylamine by rats receiving 14C-NDMA as a possible index of the extent of in-vivo denitrosation. Correcting for the proportion of labelled methylamine recovered in the urine following its administration under the conditions used for NDMA, 2.

The effect of single intravenous doses of cimetidine or ranitidine on gastric secretion.

Intravenous cimetidine, 300 mg or 400 mg, or ranitidine, 50 mg, was administered as a single dose to 36 volunteers in a randomized, crossover fashion. Aspirates of gastric juice were obtained after dosing, and the pH, titratable acidity, gastric fluid volume, and gastric acid output were determined from baseline through 71/2 hours for each subject. Each intervention significantly increased pH and suppressed hydrogen ion concentration, gastric fluid volume, and gastric acid output.