Living conditions and health promotion strategies.

The paper assesses the empirical evidence concerning the interface between living conditions and health status provided by a number of case studies of urban regeneration in London, and Brighton and Hove. These studies were carried out in the theoretical framework provided by the Cost-effectiveness in Housing Investment programme that has been seeking since 1993 to identify and measure additional 'exported' costs to services such as health, education and policing which derive from poor living conditions. A chronological study of the 'health gain' associated with the Central Stepney Single Regeneration Budget improvement to two run-down estates indicates that a seven-fold health improvement in the rate of 'illness days' experienced has taken place over a four-year period (1996-2000). This 7:1 differential was identical to that found in the synoptic comparison of illness days, and some health and policing costs, between the Stepney area and an area of improved housing in Paddington carried out in 1996. The paper presents an exploratory attempt to list and categorise in various ways the exported costs associated with poor living conditions and offers some preliminary assessment of their measurability. Finally, a number of health promoting strategies that should be borne in mind when carrying out urban renewal programmes are discussed. It is argued that the provision of satisfactory housing is a necessary, but not sufficient, condition to promote good health. Attention must also be paid to community development, especially of 'organic' activities, the quality of services especially in relation to benefits, access to healthy food, crime reduction and, critically, the promotion of jobs and the reduction of poverty.

Doping control in sports--a perspective from the 1996 Olympic Games.

Doping-control (DC) procedures, particularly as used at the 1996 Olympic Games, are described, and the role of pharmacists in DC is discussed. DC procedures must be strict and precisely followed to avoid contamination of samples, the appearance of bias, and breaches in security and confidentiality. The process of selecting athletes for testing can be random, nonrandom, or a combination of the two. Escorts are used to notify athletes of their selection, verify their identity, and accompany them to the DC station. When urine specimens are obtained for DC, the voiding process must be directly observed. The specimen is checked for pH and specific gravity and then processed for shipping to a laboratory to be analyzed for banned substances. Medication histories are also obtained, giving athletes the opportunity to declare any substance that has been taken for legitimate medical purposes. Laboratory analysis involves screening and confirmation phases. During the Atlanta Games, roughly 50 pharmacists participated in the DC program as escorts or technical officers. It is logical to involve pharmacists in DC programs because they can develop and conduct drug-testing protocols; educate athletes, coaches, and trainers about drug use and abuse; and help ensure the safe and effective use of medications. Sophisticated doping-control procedures have been developed for athletic competitions, and pharmacists have much to offer DC programs.

Excretion of bupropion in breast milk.

OBJECTIVE: To measure the excretion of bupropion and its metabolites in breast milk. A secondary objective was to determine whether the drug accumulated in the nursing infant. CASE SUMMARY: Milk and plasma samples were collected from a woman taking bupropion 300 mg/d in divided doses who was breastfeeding her 14-month-old son. A single plasma sample was collected from the infant. RESULTS: After a 100-mg dose, the peak bupropion breast milk concentration measured at two hours was 0.189 micrograms/mL. Milk-to-plasma ratios ranged from 2.51 to 8.58 over a six-hour interval. Two of three metabolites also were measured in milk. Bupropion and its metabolites were not detected in the single plasma sample obtained from the infant. CONCLUSIONS: Bupropion accumulates in human breast milk in concentrations much higher than in maternal plasma. Two metabolites are also excreted into the milk. Neither bupropion nor its metabolites were detected in the infant's plasma, indicating that accumulation did not occur in this infant.

A decade of experience with a clinical pharmacokinetics service.

The development, operation, and functions of the pharmacokinetics service at Memorial Medical Center of Long Beach (MMCLB) are described, and the data used to determine the quality and cost-effectiveness of the service are presented. Current functions of the pharmacokinetics service at MMCLB include making brief written comments about the interpretations of serum drug concentrations (SDCs) and oral recommendations to physicians on dosage adjustment; provision of written consultations with dosage recommendations; provision of drug information, education, and research; and development of drug dosing guidelines for the pharmacy and medical staff. During the 10-year existence of this service, costs have been justified on the basis of not only revenue generated by the service (in the form of "drug concentration scheduling" and "drug concentration evaluation" fees charged to patients) but also by cost savings resulting from the prevention of inappropriate, misleading, and potentially dangerous SDCs. An audit conducted in 1986 showed that the policy of having pharmacists schedule the sampling times for SDCs saves about $500,000 annually. Quality assurance has been documented by auditing compliance with and therapeutic effectiveness of dosing guidelines and by working with laboratory personnel to identify and prevent spurious SDC results and assay errors. The methods used by the pharmacokinetics service at MMCLB to document the benefits of the service have been vital in proving both its cost-effectiveness and its positive effect on patient care.

Clinical pharmacokinetics of chloramphenicol and chloramphenicol succinate.

In recent years there has been a renewal of interest in chloramphenicol, predominantly because of the emergence of ampicillin-resistant Haemophilus influenzae, the leading cause of bacterial meningitis in infants and children. Three preparations of chloramphenicol are most commonly used in clinical practice: a crystalline powder for oral administration, a palmitate ester for oral administration as a suspension, and a succinate ester for parenteral administration. Both esters are inactive, requiring hydrolysis to chloramphenicol for anti-bacterial activity. The palmitate ester is hydrolysed in the small intestine to active chloramphenicol prior to absorption. Chloramphenicol succinate acts as a prodrug, being converted to active chloramphenicol while it is circulating in the body. Various assays have been developed to determine the concentration of chloramphenicol in biological fluids. Of these, high-performance liquid chromatographic and radioenzymatic assays are accurate, precise, specific, and have excellent sensitivities for chloramphenicol. They are rapid and have made therapeutic drug monitoring practical for chloramphenicol. The bioavailability of oral crystalline chloramphenicol and chloramphenicol palmitate is approximately 80%. The time for peak plasma concentrations is dependent on particle size and correlates with in vitro dissolution and deaggregation rates. The bioavailability of chloramphenicol after intravenous administration of the succinate ester averages approximately 70%, but the range is quite variable. Incomplete bioavailability is the result of renal excretion of unchanged chloramphenicol succinate prior to it being hydrolysed to active chloramphenicol. Plasma protein binding of chloramphenicol is approximately 60% in healthy adults. The drug is extensively distributed to many tissues and body fluids, including cerebrospinal fluid and breast milk, and it crosses the placenta. Reported mean values for the apparent volume of distribution range from 0.6 to 1.0 L/kg. Most of a chloramphenicol dose is metabolised by the liver to inactive products, the chief metabolite being a glucuronide conjugate; only 5 to 15% of chloramphenicol is excreted unchanged in the urine. The elimination half-life is approximately 4 hours. Inaccurate determinations of the pharmacokinetic parameters may result by incorrectly assuming rapid and complete hydrolysis of chloramphenicol succinate. The pharmacokinetics of chloramphenicol succinate have been described by a 2-compartment model. The reported values for the apparent volume of distribution range from 0.2 to 3.1 L/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglycoside inactivation by penicillins and cephalosporins and its impact on drug-level monitoring.

The degree of in vitro inactivation of gentamicin, tobramycin, and amikacin by various penicillins and cephalosporins was investigated. Serum samples were prepared that contained one aminoglycoside and one penicillin or cephalosporin. Each aminoglycoside was combined with each of the following: penicillin, ampicillin, nafcillin, carbenicillin, ticarcillin, cephapirin, cefazolin, cefoxitin, and cefamandole. Each sample contained a final concentration of 10 micrograms/ml of gentamicin or tobramycin, or 35 micrograms/ml of amikacin, with 400 micrograms/ml of the beta-lactam antibiotic. Control samples containing only the aminoglycoside were used for comparison. Half of each mixture was frozen at -20 degrees C and the remainder was left at room temperature for 24 hours. The samples were assayed for aminoglycoside content by a radioimmunoassay and each combination was compared with its control value. Based on the results, the beta-lactams can be divided into three groups: (1) cefazolin and cefamandole, which cause little inactivation; (2) nafcillin, cephapirin, and cefoxitin, which cause moderate inactivation; and (3) penicillin, ampicillin, carbenicillin, and ticarcillin, which cause marked inactivation. In general, tobramycin was the most reactive of the three aminoglycosides studied and amikacin the most stable. The frozen samples were much less affected than those left at room temperature. Freezing samples, if there will be a delay in assaying, and choosing aminoglycoside sampling times when the beta-lactam concentration is at a trough are recommended to minimize spurious aminoglycoside level determinations due to in vitro inactivation.