The influence of an academic representative on prescribing by general practitioners.

1. The effect of providing information about medicines by a short 'sales' interview between individual general practitioners and an 'academic representative' on prescribing was investigated. 2. The promotional campaign was designed to encourage a rational approach to prescribing of non-steroidal anti-inflammatory agents in an intervention group of 101 general practitioners selected at random from the Leeds Family Practitioner Committee (FPC). The remaining general practitioners in the Leeds FPC acted as a reference group. 3. The prescribing data for each group for 5 months immediately prior to and 5 months following intervention were compared. 4. Intervention produced a significant increase (P less than 0.005) in the prescribing cost of ibuprofen, the non-steroidal promoted as first choice agent, which was sustained for at least 5 months. 5. Prescribing of the second choice agent, piroxicam, decreased in the reference group but not in the intervention group. 6. There was a decrease in the average prescribing cost of pounds 6.60 per doctor per month in the intervention group compared with the reference group.

Use of cytogenetic methods to determine mutagenic changes in the blood of pharmacy personnel and nurses who handle cytotoxic agents.

Lymphocytes of subjects from throughout the United Kingdom were studied over a two-year period beginning in January 1985 to determine the level of chromosomal damage produced by environmental exposure to cytotoxic agents. A small pilot study was conducted to determine the expected background level of chromosomal aberrations. Four groups of subjects were then recruited: pharmacy personnel who reconstituted the drugs under recommended conditions, nurses who did not reconstitute the drugs but worked on units where patients received cytotoxic chemotherapy, unexposed office workers from the same geographic location as the pharmacy personnel and nurses (negative control), and patients receiving cytotoxic drugs (positive control). Subjects completed questionnaires about smoking, viral illnesses, radiation exposure, and medication use in the past 12 months; pharmacy personnel were asked the numbers of times (1) they had handled specific drugs and (2) spills had occurred with these drugs. Lymphocytes from subjects were incubated for 48 hours, and first-division metaphases were examined for chromosome and chromatid aberrations; damage was measured as the number of aberrations per 100 cells. For a blood sample to be included in the analysis, at least 100 metaphase divisions had to be examined. Data were analyzed for 50 pharmacy staff members, 11 nurses, 12 controls, and 6 patients. Metaphase divisions in cells of the pharmacy personnel and nurses indicated no significant difference in chromosomal damage compared with the unexposed office workers. When the pharmacy, nurse, and control groups were pooled into a nonpatient group and compared with the patient group, significantly greater damage was observed in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of alcohol intake on the disposition of diphenhydramine in man.

The disposition of diphenhydramine (DPHA) and its principal metabolites was investigated in two subjects after i.v. and oral dosing. Based on these parameters the results of a multiple oral dose regimen were predicted and compared to the results obtained in these volunteers. During one dose interval of the multiple oral dose regimen, the volunteers indulged in social drinking. Comparison of this interval with a control period showed no differences in disposition. Alcohol therefore, would appear to have no effect on the disposition of DPHA.

The effect of in-vivo dispersion and gastric emptying on glibenclamide absorption from a novel, rapidly dissolving capsule formulation.

The in-vivo dispersion and gastric emptying of a novel glibenclamide dose form have been investigated using gamma-scintigraphy and related to the absorption of glibenclamide determined by measuring glibenclamide plasma concentrations. Its absorption is determined by the rate of emptying of the dose form from the stomach with the lag time between dosing and the start of gastric emptying (and hence absorption of the dose) largely dependent on the in-vivo disintegration time. The presence of food in the stomach has a marked effect on in-vivo disintegration/dispersion of the dose form and hence on the lag time between dosing and the start of absorption.

The disposition of diphenhydramine and four of its analogues in rabbits and implication for structure-activity relationship studies in drug design.

The disposition of diphenhydramine (I) and four of its ring substituted analogues, 4-bromodiphenhydramine (II), 4-methyldiphenhydramine (III), 2-methyldiphenhydramine (IV), and 4-t-butyldiphenhydramine (V), was investigated in the rabbit, during and after intravenous infusion. The concentration of each analogue was determined by gas-liquid chromatography (GLC) and the disposition parameters of clearance, volume of distribution, and elimination rate constant determined. These parameters were found to vary within the series, clearance increased in the order I less than IV less than III less than II less than V and volume of distribution in the order III less than 1 less than IV less than V less than II. These changes correlated with the Hansch hydrophobic substituent parameter: for clearance r = 0.97, for volume r = 0.7. The implication of these changes for the design of studies investigating the effects of structure on pharmacological response are discussed.

Saliva and blood pethidine concentrations in the mother and the newborn baby.

In a group of mothers who received pethidine intramuscularly during labour, drug concentrations were higher in saliva than in blood and there was a significant correlation (p < 0.001) between saliva and blood concentrations measured between 1 hour and 4 hours 20 minutes after dosage. In newborn babies, the pethidine concentrations detected in pharyngeal aspirates were higher than those in umbilical arterial or umbilical venous blood, but there was no correlation. Pethidine was also detected in the saliva from babies for 48 hours after birth. Furthermore, the appreciably higher levels in breast-fed babies suggest that such babies may receive a dose of pethidine in the milk.

Repeated investigations of cyclophosphamide disposition in myeloma patients receiving intermittent chemotherapy.

1 The disposition of cyclophosphamide was investigated in a group of myeloma patients. 2 Marked changes in clearance and volume of distribution of cyclophosphamide occurred between investigations. 3 The observed changes in disposition did not correlate with biochemical estimates of renal and hepatic function or plasma protein status.

The effect of proteolytic enzymes on the disposition of tetracycline.

The acute administration of a mixture of trypsin and chymotrypsin did not significantly affect the rate or extent of disappearance of tetracycline from the rat gut in situ, nor did chronic administration of enteric coated tablets containing trypsin and chymotrypsin to rats significantly influence the rate or extent of absorption of tetracycline compared with rats receiving enteric coated placebo tablets. Similarly, chronic enzyme administration did not effect either the systemic clearance, half life or apparent volume of distribution of intravenously administered tetracycline compared with rats receiving placebo tablets.

The disposition of cyclophosphamide in a group of myeloma patients.

The disposition of cyclophosphamide and its alkylating metabolites was investigated in a group of myeloma patients with varying degrees of renal function impairment. No correlation between renal function and clearance of cyclophosphamide or its alkylating metabolites was found. No evidence of accumulation of cyclophosphamide or alkylating activity was found in four patients receiving radiolabelled cyclophosphamide. Renal function was found to be related to the reciprocal of the area under curve of alkylating activity, indicating that this area increased as renal function decreased. In view of the large nonrenal component of alkylating activity elimination and the large inter-subject variability, it is recommended that dose of cyclophosphamide is not altered in moderate impairment of renal function.

Bioavailability of griseofulvin from a novel capsule formulation.

The in vivo availability of griseofulvin from a novel formulation has been compared with the micronized powder. The formulation technique involves the conversion of the hydrophobic surface of the drug to a hydrophilic one by treatment with a film forming polymer. This enhances the wettability of the power, and increases its dissolution rate. The results of the in vivo study show the formulation technique has increased the rate and extent of bioavailability of griseofulvin when compared with the non-treated powder.