A review of the pharmacoeconomics of pharmaceutical care.

Numerous studies have demonstrated that the therapeutic use of drugs results in adverse outcomes and contributes to high rates of morbidity and mortality. The causes of drug-related problems are multifactorial and their assessment has been based on factors such as inappropriate prescribing, inappropriate delivery, inappropriate patient behaviour, patient idiosyncrasy and inappropriate monitoring. The cost in the ambulatory setting has been estimated to exceed total prescription pharmaceutical use. Pharmaceutical care is defined as the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient's quality of life. It describes the process through which a pharmacist cooperates with a patient and other healthcare professionals in designing, implementing and monitoring a therapeutic plan that will produce specific therapeutic outcomes for the patient. This article evaluates published studies related to the economic analysis of pharmaceutical care in enhancing the value of pharmaceuticals. While numerous descriptive articles exist, our review found no studies which met accepted pharmacoeconomic criteria. A small number of studies measured process variables and/or quality of life, but only one considered costs. Barriers to optimising the economic value of pharmaceutical care were also explored. Common methodological shortcomings indicated a need for improvement in future studies. There is little published research to date which demonstrates the pharmacoeconomic benefits of pharmaceutical care. Evidence does exist that clinical pharmacy services have positive economic benefits, and it is this evidence that, at present, supports the assertion that pharmaceutical care has potential to increase the value of pharmaceuticals in society by minimising drug-related morbidity and mortality. Thus, well conducted research is required to determine the economic impact of pharmaceutical care.

Distribution and excretion of sertraline and N-desmethylsertraline in human milk.

AIMS: To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline and N-desmethylsertraline, in breast-feeding women taking sertraline for the treatment of depression. METHODS: Eight women (mean age 28 years) taking sertraline (1.05 mg kg(-1) day(-1)) and their infants (mean age 5.7 months) were studied. Sertraline and N-desmethylsertraline in plasma and milk were measured by high-performance liquid chromatography over a 24 h dose interval at steady-state. M/P values were estimated from area under the plasma and milk concentration-time curves. All milk produced was collected over the dose interval. Infant exposure was estimated as the product of actual or estimated milk production, and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. RESULTS: Mean milk production was 321 ml day(-1) (range 34-974 ml). Mean M/P values of 1.93 and 1.64 were calculated for sertraline and N-desmethylsertraline respectively. Infant exposure estimated from actual milk produced was 0.2% and 0.3% of the weight-adjusted maternal dose for sertraline and N-desmethylsertraline (as sertraline equivalents) respectively. When calculated from estimated milk production (0.15 l kg(-1) day(-1)), infant exposure was significantly greater (P<0.0001) at 0.90% and 1.32% for sertraline and N-desmethylsertraline respectively. Neither sertraline nor its N-desmethyl metabolite could be detected in plasma samples from the four infants tested. No adverse effects were observed in any of the eight infants and all had achieved normal developmental milestones. CONCLUSIONS: Irrespective of the method of calculation of infant exposure, the mean total dose of sertraline and its N-desmethyl metabolite transmitted to infants via breast-feeding is low and unlikely to cause any significant adverse effects.

Postoperative nausea and vomiting: development of a management protocol.

Postoperative nausea and vomiting (PONV) is still an important and common problem. Despite the introduction of new antiemetic drugs, the management of PONV remains difficult. In this article we describe the development and evaluation of a management protocol for PONV, which consists of a treatment algorithm accompanied by a nursing education program. Implementation of this management protocol has been well-accepted by staff, appears to have reduced delay in patient treatment and improved patient care, and has significantly reduced staff workload. It is planned to use continuous quality improvement techniques to further refine the algorithm and continue assessment of its efficacy and of patient satisfaction.

Methadone distribution and excretion into breast milk of clients in a methadone maintenance programme.

AIMS: Methadone is widely used in maintenance programs for opioid-dependent subjects. The aims of the study were to quantify the distribution and excretion of methadone in human milk during the early postnatal period and to investigate exposure of breast fed infants to the drug. METHODS: Blood and milk samples were obtained from 12 breast feeding women who were taking methadone in daily doses ranging from 20-80 mg (0.3-1.14 mg kg-1). Blood was also obtained from eight of their infants. Methadone concentration in these samples was quantified by h.p.l.c. The infants were observed for withdrawal symptoms. RESULTS: The mean (95% CI) milk/plasma ratio was 0.44 (0.24-0.64). Exposure of the infants, calculated assuming an average milk intake of 0.15 l kg-1 day-1 and a bioavailability of 100% was 17.4 (10.8-24) microg kg-1 day-1. The mean infant dose expressed as a percentage of the maternal dose was 2.79 (2.07-3.51)%. Methadone concentrations in seven infants were below the limit of detection for the h.p.l.c. assay procedure, while one infant had a plasma methadone concentration of 6.5 microg l-1. Infant exposure to methadone via human milk was insufficient to prevent the development of a neonatal abstinence syndrome which was seen in seven (64%) infants. No adverse effects attributable to methadone in milk were seen. CONCLUSIONS: We conclude that exposure of breast fed infants to methadone taken by their mothers is minimal and that women in methadone maintenance programs should not be discouraged from breast feeding because of this exposure.

Distribution and excretion of sumatriptan in human milk.

1. The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg. Drug concentrations in milk and plasma over the ensuing 8 h were measured by high-performance liquid chromatography. 2. The mean milk:plasma ratio estimated from the areas under the milk and plasma concentration-time curves (AUC) was 4.9 (95% CI 4.1-5.7), indicating a significant transfer of sumatriptan into the milk compartment. 3. The mean total recovery of drug in milk was estimated to be only 14.4 micrograms (95% CI 6.1-22.7 micrograms), or 0.24% of the 6 mg administered dose. On a weight-adjusted basis this corresponded to a mean infant exposure of 3.5% of the maternal dose (95% CI 0.3-6.7%). 4. If oral bioavailability in the infant is similar to that in adults (14%), the weight-adjusted infant dose is reduced to 0.49%. Furthermore, allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. 5. Since sumatriptan is usually administered as a single dose at infrequent intervals, the low level of excretion in breast milk suggests that continued breast feeding following its use will not pose a significant risk to the suckling infant. Even this minor exposure could be largely avoided by expressing and discarding all milk for 8 h after the dose.

Excretion of lignocaine and its metabolite monoethylglycinexylidide in breast milk following its use in a dental procedure. A case report.

The excretion of lignocaine in breast milk has been documented in a 34-year-old woman following the injection of 20 mg lignocaine for a dental alloy restoration in the right upper quadrant. Lignocaine and its primary metabolite monoethylglycinexylidide in milk and plasma were quantified by high-performance liquid chromatography. The concentration of lignocaine in milk ranged from 44-66 micrograms l-1 while that for monoethylglycinexylidide ranged from 35-41 micrograms l-1. The milk: plasma ratios for lignocaine and monoethylglycinexylidide were 1.1 and 1.8, respectively. The calculated daily infant doses for the parent drug and metabolite were both less than 0.01 mg kg-1 day-1. With the exception of very rare allergic reactions, these levels of infant exposure are extremely low and of no toxicological significance. Nursing mothers receiving lignocaine for standard dental procedures can be advised that continuation of breast feeding is safe.

The excretion of dothiepin and its primary metabolites in breast milk.

1. The excretion of dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide into breast milk was studied in eight women. Exposure to drug was measured in five of their infants, and possible drug-related effects were assessed in all eight infants. 2. Using pre-feed milk samples mean (+/- s.e. mean) milk:plasma (M:P) ratios were 0.78 +/- 0.12, 0.85 +/- 0.16, 1.18 +/- 0.29 and 1.86 +/- 0.29 for dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide, respectively. In post-feed milk samples, the mean M:P ratio for dothiepin (1.59 +/- 0.32) was significantly greater (P less than 0.05) but M:P ratios for the metabolites were similar. 3. Mean total calculated infant daily doses, (in dothiepin equivalents and as a percent of the maternal dose) were 0.58% for dothiepin, 0.23% for nordothiepin, 2.47% for dothiepin-S-oxide, and 1.17% for nordothiepin-S-oxide. 4. Plasma samples were obtained from five infants. In one, both dothiepin and nordothiepin were below their minimum quantifiable levels (2 micrograms l-1) while in four others both dothiepin-S-oxide and nordothiepin-S-oxide were below their minimum quantifiable levels (10 micrograms l-1). No adverse effects were found in any of the eight infants. 5. Use of dothiepin by depressed mothers is unlikely to be a significant hazard to their breast-feeding infants.

Excretion of indomethacin in breast milk.

1. The excretion of indomethacin into breast milk and subsequent exposure of infants was studied in 16 women and seven of their infants. The median milk:plasma ratio in seven patients where there were measurable drug concentrations in both milk and plasma was 0.37. 2. Total infant dose, assuming a daily milk intake of 150 ml kg-1 and 100% absorption, ranged from 0.07% to 0.98% (median = 0.18%) of the weight adjusted maternal dose. 3. Plasma samples were obtained in seven infants. In six of these, indomethacin concentrations were below the sensitivity of the assay (less than 20 micrograms l-1), while one infant had a plasma indomethacin concentration of 47 micrograms l-1. 4. No adverse effects due to indomethacin were reported in the infants.