John Knowles

Clinical pharmacokinetics of lorazepam; II. Intramuscular injection

A single dose of 4 mg of lorazepam was injected into the deltoid muscles of six healthy male volunteers. Multiple venous blood sampies were drawn during 48 hr after the dose and all urine was collected for 24 hr after the dose. Concentrations of lorazepam and its major metabolite, lorazepam glucuronide, were determined by electron‐capture gas‐liquid chromatography. Lorazepam was rapidly absorbed from the injection sire, reaching peak concentrations within 3 hr. Mean pharmacokinetic pamrameters for unchanged lorazepam were: apparent absorption half‐life: 21.2 min: elimination half‐life: 13.6 hr; volume of distribution: 0.9 L/kg; total clearance: 58.2 ml/min. Lorazepam glucuronide rapidly appeared in plasma, reached peak concentrations within 12 hr of the dose, then was eliminated approximately in parallel with the parent drug. Within 24 hr a mean of 47.6% of the dose was recovered in the urine as lorazepam glucuronide and less than 0.5% was recovered as unchanged lorazepam.

Why are Married Men Working So Much

We document a negative trend in the leisure of men married to women aged 25-45, relative to that of their wives, and a positive trend in relative housework. We develop a simple bargaining model of marriage, divorce and allocations of leisure-time and housework. Calibration to US data shows the trend in the wage gender gap explains most of the trend in relative leisure, but has little effect on married womens labor supply, which appears to be due mainly to the trend in the price of home equipment.

CRIME MINIMISATION AND RACIAL BIAS: WHAT CAN WE LEARN FROM POLICE SEARCH DATA?*

Are variations in the success rate of searches by race informative about racial bias if police are motivated by crime minimization rather than success-rate maximization? We show that the basic idea of extracting information from hit rates may still be valid, provided one can verify some simple restrictions on the joint distribution of criminality by race. We also extend these results to the case where the police minimize the rate of unpunished crime.

Oxaprozin disposition in renal disease

Effects of renal disease on the disposition kinetics of oxaprozin, a nonsteroidal antiinflammatory analgesic, were assessed in 15 subjects who were normal, renally impaired, or who had been undergoing hemodialysis. Oral dose clearance (Cloral), volume of distribution at steady‐state (Vssd), and elimination half‐life (tl/2) did not substantially differ among the three groups. Mean fraction unbound oxaprozin in plasma (fup) increased from 0.08% in the normal group to 0.18% and 0.28% in the two azotemic groups. Consequently, unbound drug kinetic parameters, including intrinsic clearance (Clint) and Vssdu of unbound drug were reduced from 2.9 l/hr/kg and 193 l/kg in normal subjects to approximately 1.6 l/hr/kg and 91 l/kg in azotemic patients. The smaller volume of distribution is consistent with a decrease in oxaprozin tissue binding in azotemia. The decreased plasma and tissue binding and lower Clint suggest that, in the treatment of azotemic patients with rheumatoid arthritis, the dose of oxaprozin should begin at 600 mg once a day.

The Timing of Births: A Marriage Market Analysis

We argue that one of the key channels linking the labor and marriage markets is the decision of when to become a parent. We develop art equilibrium model of marriage, divorce, and human capital accumulation that allows for differential timing of fertility. We calibrate the model to US panel data and analyze the effects of raising womens wages relative to mens, and increasing the rate of return to experience for women. We find that an increase in the returns to experience for women is causes an increase in fraction of children born to women over age 30, and that raising women wages reduces marriage rates.

A Specific and Highly Sensitive Method for the Determination of Protriptyline in Body Fluids and Tissues

Abstract Protriptyline, a tricyclic antidepressant, was converted to its heptafluorobutyramide using heptafluorobutyrylimidazole as the acylating agent. Conditions for the gas chromatography of the derivative and its quantitation by an electron capture detector were established. The smallest detectable amount of the protriptyline derivative was 0.05 nanogram. Isolation and purification procedures were devised which permit the determination of the drug in biological materials without interference from reagents, drug metabolites or naturally occurring substances. Protriptyline extracted from plasma, erythrocytes, urine and tissues was determined in concentrations as low as 10 nanograms/ml.

Determination of Meperidine in Human Plasma and Urine by Gas-Liquid Chromatography

Abstract A highly sensitive method for the determination of meperidine and normeperidine in biological fluids is presented. Concentrations as low as 5 ng meperidine and 25 ng normeperidine per ml of sample can be determined. The recovery of meperidine from control plasma and urine was 91.3 to 102.5% and the recovery of normeperidine was 64.7 to 82.8%. The method has been successfully used for the determination of meperidine in human plasma and urine and of normeperidine in human urine.

Determination of cycloleucine in biological fluids

Abstract A method for quantitation of cycloleucine in biological fluids is described. Cycloleucine is oxidized to cyclopentanone by ninhydrin. The cyclopentanone formed is extracted into chloroform and determined by GLC. The method is accurate, convenient, rapid, and free of interference by other constituents of urine or serum.

CLINICAL PHARMACOKINETICS OF LORAZEPAM III INTRAVENOUS INJECTION PRELIMINARY RESULT

Four healthy male volunteers received 5 mg lorazepam as a single intravenous injection. Concentrations of lorazepam and its glucuronide metabolite were determined in multiple venous blood samples drawn during the 48 hours after dosing and in all urine collected during 96 hours after the dose. Mean pharmacokinetic parameters for lorazepam were: apparent elimination half-life, 13.2 hours; volume of distribution, 0.84 liter/kg; total clearance, 55.3 ml/min. Lorazepam glucuronide, the major metabolic product of lorazepam, promptly appeared in blood, reached peak levels within 6 hours of the dose, then declined in parallel with the parent compound. A mean of 69 per cent of the dose was recovered in urine as lorazepam glucuronide.