Peter J. Ambrose

Accuracy of Oral Liquid Measuring Devices: Comparison of Dosing Cup and Oral Dosing Syringe

Background: Previous studies have found that teaspoons are commonly used to administer liquid medications to children. The capacity of household teaspoons ranges from 1.5 mL to 9 mL, potentially leading to errors in dosing. There are few studies evaluating alternative measuring devices. Objective: To assess adult consumers’ previous experience with measuring devices for oral liquids, compare the accuracy of an oral syringe with that of a dosing cup, and determine consumer perceptions of accuracy and ease of use of an oral syringe and a dosing cup. Methods: Individuals at least 18 years of age were shown a picture of 5 commonly used measurement devices and asked their perceptions of and experience with the devices. They were then asked to measure a 5 mL (1 teaspoon) dose of Tylenol (acetaminophen) suspension, using the EZY Dose oral syringe and the dosing cup provided by the manufacturer. An acceptable dose was defined as 5.0 ± 0.5 mL. Following the measurement, participants completed a 5 item survey that assessed their perceptions of the accuracy and ease of use of the syringe and dosing cup. Results: A total of 96 subjects completed the study. Participants more commonly reported use of droppers (68%), dosing cups (67%), and teaspoons (62%) versus cylindrical spoons (49%) or oral syringes (49%) for measuring oral liquids. Sixty-four (66.7%) subjects measured an acceptable dose using the syringe versus 14 subjects (14.6%) using the cup (p < 0.001). The mean volumes ± SD measured with the syringe and cup were 4.5 ± 0.7 mL and 6.3 ± 0.7 mL, respectively (p < 0.001). After using both devices, the majority of subjects believed that the syringe (80%) and cup (71%) would measure an accurate dose. Most (87%) participants perceived that the cup was easy to use; 63% believed that the syringe was easy to use. Conclusions: Droppers and dosing cups were the most commonly used devices in the home for measuring liquid medications. Subjects were more likely to measure an acceptable dose with an oral syringe when compared with a dosing cup. However, a large proportion of study participants were unable to measure an accurate dose with either device. Community pharmacists should educate caregivers on the selection and proper use of measuring devices to improve the accuracy of medication administration in the home.

Blood Pressure and Heart Rate Effects following a Single Dose of Bitter Orange

Background: The ingredients of numerous “ephedra-free” dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). Objective: To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. Methods: In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Natures Way Bitter Orange—a 900 mg dietary supplement extract standardized to 6% synephrine—or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. Results: SBP after bitter orange was significantly increased versus placebo at hours 1–5 (p < 0.0001); the peak difference was 7.3 ± 4.6 mm Hg. Although the baseline DBP was higher than after administration of both placebo and bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p ≤ 0.02); the peak difference was 2.6 ± 3.8 mm Hg. HR was significantly increased after bitter orange versus placebo for hours 2–5 (p < 0.01); the peak difference was 4.2 ± 4.5 beats/min. Conclusions: SBP, DBP, and HR were higher for up to 5 hours after a single dose of bitter orange versus placebo in young, healthy adults.

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 (μg/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 infants plasma, indicating that accumulation did not occur in this infant.

Excretion of metformin into breast milk and the effect on nursing infants

OBJECTIVE: To determine whether metformin is excreted into breast milk and whether this exposure adversely affects the blood glucose of nursing infants. METHODS: Seven women were started on metformin 500 mg twice daily on the first day after cesarean delivery. Breastfeeding was started at the same time. Two women were excluded. Two other women stopped breastfeeding for personal reasons unrelated to the drug therapy, but did provide serum and milk samples, because they regularly pumped their breasts to maintain lactation. Peak and trough serum and milk samples were drawn between postoperative days 4 and 17. In 3 infants, blood was drawn for glucose determination at the same time as the maternal samples. RESULTS: The trough milk concentration in 1 subject was below the assay detection limit. Excluding this subject, the mean peak and trough serum metformin concentrations were 1.06 &mgr;g/mL (range 0.68–1.90 &mgr;g/mL) and 0.42 &mgr;g/mL (range 0.26–0.51 &mgr;g/mL), respectively, whereas the mean peak and trough metformin concentrations in breast milk were 0.42 &mgr;g/mL (range 0.38–0.46 &mgr;g/mL) and 0.39 &mgr;g/mL (range 0.31–0.52 &mgr;g/mL), respectively. The mean milk:serum ratio was 0.63 (range 0.36–1.00) and the mean estimated infant dose as a percentage of the mothers weight-adjusted dose was 0.65% (range 0.43–1.08%). In 3 infants, the blood glucose concentrations 4 hours after a feeding were within the normal limit, ranging from 47–77 mg/dL. CONCLUSION: Metformin is excreted into breast milk, but the amounts seem to be clinically insignificant. No adverse effects on the blood glucose of the 3 nursing infants were measured. LEVEL OF EVIDENCE: III

Drug use in sports: a veritable arena for pharmacists.

OBJECTIVE To describe opportunities and obligations for pharmacists regarding doping control in sports, and to present information and resources on drugs and dietary supplements that are popular among athletes for performance enhancement. DATA SOURCES Sports medicine journals and articles in English obtained from Medline (1966 through June 2003) using the search terms doping in sports, drugs in sports, dietary supplements, sports, amphetamine, stimulants, ephedrine, ephedra, caffeine, anabolic steroids, human growth hormone, erythropoietin, darbepoetin, androstenedione, dehydroepiandrosterone, and creatine. Information was also obtained from sports-governing agencies, such as the National Collegiate Athletic Association and the International Olympic Committee. STUDY SELECTION Studies and reports that were credible and scientifically sound that evaluated the ergogenic effects of drugs and dietary supplements. DATA EXTRACTION By the author. DATA SYNTHESIS Pharmacists can participate in doping control programs in a number of ways. Pharmacists also have an obligation when counseling, advising, and treating athletes to help them avoid banned substances. Athletes use a host of drugs for their performance-enhancing effects, many of which are banned by major sports-governing bodies. Myriad dietary supplements are marketed to athletes, claiming to have ergogenic effects. Some of these popular supplements have proven performance-enhancing effects, while others do not. Adverse effects of these drugs and dietary supplements are discussed. CONCLUSION A variety of drugs and dietary supplements have proven performance-enhancing effects in athletes. However, many of these substances have adverse effects and are banned by various sports-governing organizations. Pharmacists can play a key role in participating in doping control programs, and can prevent athletes from inadvertently consuming a banned substance.

Use of Duloxetine in Pregnancy and Lactation

Objective: To report a case of a woman who used duloxetine during pregnancy and breast-feeding. Case Summary: A 29-year-old woman was treated with duloxetine for depression during the second half of an uncomplicated gestation. She gave birth at term to a healthy female infant. A cord blood sample was obtained at birth. The mother continued the antidepressant while exclusively breast-feeding her infant. One month later, we collected blood and milk samples from the mother and a single blood sample from the infant. All samples were analyzed for the presence and concentrations of duloxetine. Discussion: Duloxetine crosses the placenta at term and is excreted into breast milk. No evidence of developmental or other type of toxicity was observed in the infant at birth or during the first 32 days after birth. The published literature detailing human pregnancy experience with this antidepressant is limited to 11 cases in which women became pregnant while taking duloxetine. In 10 cases, the drug was discontinued when pregnancy was diagnosed and no outcome data were reported. In the eleventh case, an infant exposed to duloxetine 90 mg/day developed neonatal behavioral syndrome. One study examined the excretion of duloxetine into breast milk, but the mothers discontinued nursing for the study. In the present case, no adverse effects from exposure to the drug in milk were noted in the exclusively breast-fed infant. The possibility of functional/neurobehavioral deficits appearing later in life cannot be excluded because long-term follow-up has not been conducted in infants exposed to duloxetine in utero or during nursing. Conclusions: No developmental toxicity or other signs of toxicity were observed in an infant exposed to duloxetine during the second half of gestation and during breast-feeding in the first 32 days after birth. However, the possibility of functional/neurobehavioral deficits appearing later in life cannot be excluded.

Development Needs of Volunteer Pharmacy Practice Preceptors

Objective. To determine the training needs and interests of volunteer pharmacy preceptors. Methods. Volunteer preceptors (n=576) were surveyed on various aspects of precepting and their needs related to additional training. Results. Two hundred thirty-six preceptors (40.9%) responded. Preceptors were less confident about enforcing attendance policies, identifying and managing unmotivated or failing students, identifying dishonesty or plagiarism, and handling conflict. While only 29.5% of respondents agreed that having an APPE student decreased their overall workload, approximately half (48.1%) indicated that student pharmacists helped them complete their daily tasks and 67.8% agreed that APPE students extended patient care. Respondents who had received training were significantly more confident than preceptors who had not received training in their abilities to clarify expectations, evaluate a students knowledge, and foster skills related to critical thinking and problem solving. Conclusions. Training programs for pharmacy preceptors are effective; however, important areas in which additional training is needed or desired were identified among both new and experienced preceptors.

Gentamicin dosing in postpartum women with endometritis

Postpartum women receiving gentamicin for endometritis were studied to determine if selective determination of gentamicin serum levels was cost-effective in terms of safety and efficacy. The women were randomized into two groups of 30 patients each. In the control group gentamicin serum levels were determined after the third dose. In the study group, levels were determined only if renal dysfunction was evident or if the patient failed to respond to therapy. Determination of serum levels did not assure a better therapeutic outcome in either group, as measured by hospital stay, duration of treatment, total cost of antibiotics, and hospital readmissions. Although pharmacokinetic dosing equations were used, the use of 1.75 mg/kg every 8 hours based on actual body weight in patients with average heights and weights would have produced acceptable results. We conclude that routine monitoring of gentamicin serum levels is not required in otherwise healthy postpartum women with endometritis.

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 μ/ml of gentamicin or tobramycin, or 35 μ/ml of amikacin, with 400 μg/ml of the β-lactam antibiotic. Control samples containing only the aminoglycoside were used for comparison. Half of each mixture was frozen at −20°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 β-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 β-lactam concentration is at a trough are recommended to minimize spurious aminoglycoside level determinations due to in vitro inactivation.

Clinical Application and Evaluation of Vancomycin Dosing in Adults

Objective: To evaluate the accuracy of a vancomycin dosing method (study method) in estimating volume of distribution (Vd) and clearance of vancomycin (Clvanco) and the frequency with which it would provide serum vancomycin concentrations (SVCs) within a specified range compared with other published methods. Methods: One hundred and seven patients with 108 pairs of SVCs were used to calculate patient-specific Vd and Clvanco. Based on these patient-specific Vd and Clvanco values, the predictive ability of the estimated parameters from the study dosing method (Vd [L] = 0.17 [age] + 0.22 [actual body weight] + 15; Clvanco = creatinine clearance) was evaluated against three previously published pharmacokinetic dosing methods, using predictive performance analysis (precision and bias). Furthermore, the patient-specific pharmacokinetic parameters were used to simulate steady-state peak and trough SVCs, using first-order pharmacokinetic equations from doses derived from the study method, the three different pharmacokinetic methods, and two other published dosing schemes. The frequency with which each method would have achieved target peak and trough SVCs was determined. Results: The study method was found to be more precise and less biased (p < 0.05) than comparative methods in predicting vancomycin Vd and Clvanco. The study method also resulted in a higher frequency of steady-state peak and trough SVCs within the target range specified. Conclusions: The study method presented here provided a reliable estimation of vancomycin pharmacokinetic parameters that was easily applied to various patient populations to individualize vancomycin dosing, and frequently yielded SVCs within a predictable and desired range.