The disposition of chlordiazepoxide (Librium) and diazepam (Valium), compounds which are initially degraded by oxidative processes, differs from that of oxazepam (Serax) and lorazepam (Ativan, drugs which are inactivated by conjugation with glucuronic acid. Liver disease and cimetidine impair the elimination of the former agents, but not the latter two benzodiazepines. In addition, ethanol inhibits the metabolism of chlordiazepoxide and diazepam. The present studies were performed to determine the effect of short-term ethanol administration on glucuronidation and elimination of lorazepam in dogs and humans. Because, in dogs, lorazepam has a high extraction ratio (approximately 0.9) with an anticipated large presystemic elimination, the influence of ethanol on the presystemic (first-pass) elimination of lorazepam was determined. Administration of p.o. lorazepam to five healthy dogs 1 hr after i.v. saline or ethanol (3 gm/kg) reduced the presystemic elimination of lorazepam by 52% (p less than 0.05). In man, lorazepam has a low (approximately by 0.05) extraction ratio and only a small first-pass effect. Short-term administration of ethanol (0.8 gm/kg followed by 0.5 gm/kg p.o. every 5 hr for four doses) reduced i.v. lorazepam clearance by 18% (p less than 0.03). In dogs and man, ethanol did not significantly alter lorazepam t1/2, plasma protein binding, or distribution volume (Vd beta). The results suggest that short-term ethanol administration impairs the conjugation of lorazepam in dogs and man.

Adult↗

PubMedDate not supplied

Differential effects of oral contraceptive steroids on the metabolism of benzodiazepines.

The effects of oral contraceptive steroids (OCS) on the disposition and elimination of lorazepam, oxazepam, and chlordiazepoxide were examined. Lorazepam and oxazepam are metabolized via glucuronidation while chlordiazepoxide is metabolized by oxidation in the liver. The disposition and elimination of lorazepam, oxazepam, and chlordiazepoxide was studied in females not taking OCS and females taking OCS (norethindrone acetate, 1 mg; ethinyl estradiol, 50 micrograms) for 6 months or more. The t1/2 (beta) for lorazepam was significantly reduced in women taking OCS (6.0 +/- 3.1 vs. 14.0 +/- 6.2 hr) (p less than 0.005) as compared to controls, and the t1/2 (beta) for oxazepam was reduced in women taking OCS (7.71 +/- 3.23 vs. 12.09 +/- 5.08 hr) as compared to controls, but did not reach statistical significance. The plasma clearance of both lorazepam and oxazepam was significantly increased in women taking OCS [(288.9 +/- 165.9 vs. 77.5 +/- 3.29 ml per min) (p less than 0.01) and (251.2 +/- 106.9 vs. 97.86 +/- 69.4 ml per min) (p less than 0.01), respectively] as compared to controls. The volumes of distribution of lorazepam and oxazepam were significantly increased in women taking OCS (p less than 0.05) while plasma binding of these drugs was similar in both groups. In contrast, the t1/2 (beta) of chlordiazepoxide was significantly prolonged (20.58 +/- 8.08 vs. 11.63 +/- 5.91 hr) (p less than 0.05), and the plasma clearance was significantly reduced (13.41 +/- 4.69 vs. 33.22 +/- 12.37 ml per min) (p less than 0.05) in the OCS group as compared to controls. The volumes of distribution of chlordiazepoxide were similar in both groups, and the plasma binding of chlordiazepoxide tended to be lower in the OCS group but did not reach statistical significance. We conclude that OCS exert a differential effect on the elimination of benzodiazepines, whereby oxidation of chlordiazepoxide is impaired while the glucuronidation of lorazepam and oxazepam is enhanced by OCS.

Adult↗

PubMedDate not supplied

Magnetic resonance imaging in patients with unstable angina: comparison with acute myocardial infarction and normals.

The role of magnetic resonance imaging in characterizing normal, ischemic and infarcted segments of myocardium was examined in 8 patients with unstable angina, 11 patients with acute myocardial infarction, and 7 patients with stable angina. Eleven normal volunteers were imaged for comparison. Myocardial segments in short axis magnetic resonance images were classified as normal or abnormal on the basis of perfusion changes observed in thallium-201 images in 22 patients and according to the electrocariographic localization of infarction in 4 patients. T2 relaxation time was measured in 57 myocardial segments with abnormal perfusion (24 with reversible and 33 with irreversible perfusion changes) and in 25 normally perfused segments. T2 measurements in normally perfused segments of patients with acute myocardial infarction, unstable angina and stable angina were within normal range derived from T2 measurements in 48 myocardial segments of 11 normal volunteers (42 +/- 10 ms). T2 in abnormal myocardial segments of patients with stable angina also was not significantly different from normal. T2 of abnormal segments in patients with unstable angina (64 +/- 14 in reversibly ischemic and 67 +/- 21 in the irreversibly ischemic segments) was prolonged when compared to normal (p less than 0.0001) and was not significantly different from T2 in abnormal segments of patients with acute myocardial infarction (62 +/- 18 for reversibly and 66 +/- 11 for irreversibly ischemic segments). The data indicate that T2 prolongation is not specific for acute myocardial infarction and may be observed in abnormally perfused segments of patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMedDate not supplied

Effects of nicotine and nicotine/ethanol on human placental amino acids transfer.

Ethanol abuse and smoking during pregnancy both result in decreased offspring weight. One explanation for this may be impaired placental nutrient transport. This study assessed this possibility utilizing the 4-hr perfused human placental system and human placental vesicles exposed to "physiological," 0.2 microM and large (about 20 microM) nicotine concentrations alone, as well as nicotine combined with ethanol, 200 or 400 mg/ml, for up to 48 hr. Two nonmetabolizable amino acids, alpha-aminoisobutyric acid (AIB) and cycloleucine (CLEU) were used as probes. Nicotine was measured by gas chromatography in the placental perfusion system and vesicles and verified as to concentration. There was no statistically significant evidence of decreased transport of these amino acids with exposure to nicotine alone or nicotine and ethanol together in either test system. Thus, brief exposure to nicotine and ethanol does not impair amino acid transport by the human placenta.

Amino Acids↗

PubMedDate not supplied

MRI of malignant fibrous histiocytoma of the spermatic cord.

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Genital Diseases, Male↗

PubMedDate not supplied

Periodontal prognosis.

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Periodontal Diseases↗