Determination of lamivudine, zidovudine, and nevirapine in capillary blood sampled on filter paper by LC.

A bioanalytical method for determination of lamivudine (3TC), zidovudine (AZT), and nevirapine (NVP) in 100 microL capillary blood applied onto sampling paper has been developed and validated. The antiretroviral drugs (ARV) were analyzed by reversed phase gradient liquid chromatography with UV detection. Separation was performed on a Zorbax SB C(8) (250 x 4.6 mm) column with a two-step gradient: (i) methanol-0.05 mol/L acetic acid-sodium acetate buffer (pH 3.95, 15:85 v/v) and (ii) methanol-0.05 mol/L acetic acid-sodium acetate buffer (pH 3.95, 50:50 v/v) with a flow rate of 1.0 mL/min. UV detection was performed at 260 nm. Total assay precisions were 6.3, 4.7, and 4.9% for 3TC at 0.34, 0.69, and 3.9 microg/mL, and 5.1, 5.5, and 3.2% for AZT at 0.40, 0.80, and 4.5 microg/mL. For NVP, total assay precisions were 5.2, 8.3, and 3.5% at 2.6, 4.5, and 8.8 microg/mL. Lower limit of quantifications (LLOQ) were 0.11 and 0.13 microg/mL for 3TC and AZT where the precisions were 2.0% for both the analytes. For NVP, LLOQ was 1.3 microg/mL where precision was 2.6%. Concentrations were determined for 10 h for two subjects receiving standard twice daily antiretroviral therapy containing 3TC, AZT, and NVP. Maximum 3TC concentrations were 2.5 and 2.8 microg/mL for subject 1 and 2, respectively. For AZT, maximum concentrations were 1.8 and 1.1 microg/mL while being 15 and 9.6 microg/mL for NVP. Pre-dose trough concentration of NVP was 11 microg/mL for subject 1 and 9.6 microg/mL for subject 2.

Improved efficacy with amodiaquine instead of chloroquine in sulfadoxine/pyrimethamine combination treatment of falciparum malaria in Uganda: experience with fixed-dose formulation.

Amodiaquine (AQ) is an affordable compound, chemically related to chloroquine (CQ) but often effective against CQ resistant Plasmodium falciparum. In Uganda, a pre-packed fixed-dose combination of CQ plus sulfadoxine/pyrimethamine (CQ+SP) called Homapak is used in the home based management of fever program (HBM). We performed a single blind randomized trial to determine the efficacy of AQ+SP in comparison with the fixed-dose CQ+SP (Homapak) in the treatment of uncomplicated falciparum malaria in Ugandan children aged 6 months to 5 years. The study was done in 2004 at Walkuba Health Center, a sub-urban area in Jinja district, Uganda. Primary outcome was the day 14 per protocol clinical and parasitological response according to the WHO. A total of 183 children were included (mean age 28 months) and 90% completed 28 days of follow up. The day 14 adequate clinical and parasitological response was 70.9% for CQ+SP and 97.4% for AQ+SP (p<0.001). In those given CQ+SP, treatment failure rates for the 6 months to 2 years age group were much higher (48.2%) than in the older children (18.2%, p=0.004). The day 28 PCR adjusted parasitological failure rates were also higher in the CQ+SP (31.3%) than in the AQ+SP group (13.1%) (p=0.003), with a higher gametocyte carriage among the CQ+SP group. We conclude that the efficacy of AQ+SP was significantly superior to the fixed-dose CQ+SP (Homapak), particularly among the youngest children. Thus, AQ could be used instead of CQ in combination with SP to improve the effectiveness against falciparum malaria in Uganda.

Pharmacokinetic interactions between chloroquine, sulfadoxine and pyrimethamine and their bioequivalence in a generic fixed-dose combination in healthy volunteers in Uganda.

BACKGROUND: A pre-packaged fixed-dose formulation of chloroquine (CQ) and sulfadoxine/pyrimethamine (S/P) combination (Homapak) is widely used for the treatment of falciparum malaria in Ugandan children. It is however a product whose pharmacokinetics and interactions have not been studied. OBJECTIVES: To explore possible pharmacokinetic interactions between CQ and S/P during co-administration, and to determine their bioavailability in the locally made Homapak compared to the Good Manufacturing Practice (GMP) made formulations. METHODS: Thirty-two adult healthy volunteers were randomized into four groups and given single oral doses of fixed-dose CQ+S/P combination (Homapak), or GMP formulations of S/P (Fansidar), CQ (Pharco), or their combination. Plasma samples were followed for 21 days, analysed by HPLC-UV methods, with pharmacokinetic modeling using the WinNonlin software. RESULTS: Sulfadoxine in Homapak was more rapidly absorbed (ka = 0.55 h(-1)) than in Fansidar + CQ (ka = 0.27 h(-1), p=0.004), but not more than S in Fansidar alone group (ka = 0.32 h(-1), p=0.03). No significant differences were observed in the other pharmacokinetic parameters of S, P and CQ when given together or separately. The relative bioavailability of CQ and S in Homapak showed bioequivalence to reference formulations. CONCLUSIONS: There were no pharmacokinetic interactions between CQ, S and P when the compounds were given together, however, more investigations would be needed to explore this further. Compared with GMP made drugs, both S and CQ are bioequivalent in Homapak, the Ugandan made fixed-dose formulation. Furthermore, the absorption of S was more rapid which could be advantageous in malaria treatment.

Impact of decentralization on health services in Uganda: a look at facility utilization, prescribing and availability of essential drugs.

INTRODUCTION: Uganda began implementation of a structural adjustment programme (SAP) in July 1994 in order to improve social services. The decentralization of health services administration to district level was intended to improve the quality of health services and pharmaceutical supplies in the hospitals, with resultant increase in the level of utilization of health facilities. OBJECTIVE: This study evaluated the impact of the decentralization policy on health facility utilization; availability of essential drugs, and prescribing patterns for acute respiratory infections (ARI), diarrhoea, and malaria in two district hospitals in Uganda. DESIGN: Mixed method evaluation design, involving both quantitative and qualitative methods. Time series analyses of data from utilization, pharmacy stock, and prescription records before and after the policy change. Key informant interviews and focus group discussions to obtain information on perceptions and attitude of stakeholders on the process of the policy implementation. STUDY SETTING AND POPULATION: The study was conducted in two district hospitals in northern Uganda. A total of seven years of utilization and pharmacy stock data including 5040 patient records from the hospitals were analysed retrospectively. In-depth interviews were conducted among 11 politicians from each district; 100 open-ended questionnaires were administered to patients in each hospital; 86 health care workers were interviewed using semi-structured questionnaires; and focus group discussions were conducted with 23 health care providers. MAIN OUTCOME MEASURES: Facility utilization was evaluated by average monthly attendance in the outpatient department and paediatric ward admissions. Availability was assessed as average number of drugs per month. Prescribing indicator outcomes included: for malaria, percent chloroquine tablets and percent chloroquine injection; for ARI, percent receiving antibiotics or injections; for diarrhoea, use of oral rehydration salts (ORS), antidiarrhoeal mixtures, and antibiotics. The average number of drugs prescribed assessed polypharmacy. RESULTS: There was a general increase in patient attendance in both hospitals, although the initial increase later declined in Apac. Drug availability was erratic and not always adequate. The situation was better in Lira where funding for drug procurement was more accessible. Prescribing patterns varied, with improvement in some indicators, while others showed no change or even worsened. CONCLUSIONS: The decentralization policy led to increased utilization of health facilities. The perception was that the policy was good because it "empowered the community in terms of creating a sense of responsibility in the stakeholders, and a sense of ownership that facilitated sustainability" of public institutions. In spite of the views expressed by the stakeholders, the policy failed to improve drug shortages, inefficient utilization of resources, and low morale among hospital staff. Staff should be re-trained and better remunerated in order to cope with the implementation of the policy. Local politicians should clearly understand their roles and responsibility under the new policy. Efficient utilization of funds at all levels of the district administrative structures should be ensured.

Impact of an educational intervention to improve prescribing by private physicians in Uganda.

INTRODUCTION: Private physicians in urban Uganda treat a large percentage of common adult illnesses. Improving their prescribing would not only encourage more rational drug use, but also reduce costs to patients. Interventions to improve drug use are generally more successful when face-to-face educational methods are included. OBJECTIVES: To determine the effectiveness of a face-to-face educational intervention on the treatment of acute respiratory infections (ARI), malaria, and non-dysenteric diarrhoea by private physicians in three urban areas of Uganda. METHODS: The study used an intervention with comparison group design to evaluate the impact of the educational intervention. A total of 108 private physicians was divided into intervention (n = 30) and control (n = 78) groups. Surrogate patients, trained to simulate presenting symptoms and signs of the target conditions, were used to collect data on the medical practices and prescribing behaviours of the physicians. Intervention physicians were invited to a one-day interactive educational seminar facilitated by local opinion leaders that covered principles of rational drug use and the National Standard Treatment Guidelines for treating the target conditions. Physicians were also provided with data about baseline practices. RESULTS: Baseline data indicated high rates of inappropriate treatment practices by both intervention and control groups. There was nearly universal antibiotic use for ARI (over 90%), high rates of injections recommended for malaria (over 30%), and high rates of polypharmacy (over thee drugs per patient). After the intervention, some significant improvements in key practices were observed in the intervention group. Compared to control physicians, antibiotic prescribing for ARI decreased by 23% in the intervention group, use of combination products for malaria declined by 28%, there were trends towards better adherence to guidelines for ARI and malaria, and marginal decreases in drug costs. However, the overall impacts of the intervention were limited, especially on quality indicators concerning history taking, adequate examination, and advice to patients. CONCLUSION: The face-to-face educational intervention resulted in some small improvements in key prescribing practices of private physicians. However, an intervention that involved repeated contacts with prescribers and which addressed economic considerations would be needed to obtain larger improvements. Private physicians need to be sensitized to and encouraged to use the National Standard Treatment Guidelines, and attempts to improve their prescribing should be supported by community education.

A comparison of prescribing practices between public and private sector physicians in Uganda.

INTRODUCTION: Previous studies in the public sector in Uganda have demonstrated major prescribing problems due to polypharmacy and irrational use of antibiotics and injections. Little is known about prescribing in the private sector although there is little government regulation influencing practice in this sector. The introduction of policies such as the Uganda National Standard Treatment Guidelines (UNSTG) was expected to improve prescribing practices in the public and private sectors. This paper measures appropriateness of prescribing practices in the public and private sectors in Uganda for the treatment of Acute Respiratory Infections (ARI) and malaria in adult patients. DESIGN AND SAMPLING: We combined a prospective survey of treatment for simulated patients presenting with symptoms of malaria and ARI in 119 randomly selected private clinics and a retrospective survey of 600 prescription records for malaria and ARI (300 for each condition) randomly selected from 10 public health units in the Kampala, Masaka, and Jinja urban areas. OUTCOME MEASURES: Percentage of drug appropriately prescribed in each condition, % injection prescription, percentage antibiotic prescription, average number of drugs per case, average standardized cost per prescription, distribution of types of drugs prescribed. RESULTS: The overall appropriateness of prescribing for ARI and malaria was poor in both public and private sectors. Treatment of malaria was significantly less appropriate in the public sector compared to the private sector (14% vs. 27%, p = 0.002), with injectable chloroquine much more commonly prescribed. Prescribing of antibiotics for ARI was nearly universal in both sectors, with some prescriptions containing up to three antibiotics; newer, more expensive antibiotics were more commonly prescribed in the private sector. Polypharmacy and unnecessary prescribing of vitamins were common in both conditions and both sectors. CONCLUSIONS: Prescribing for adult malaria and ARI by both private and public practitioners did not conform to the UNSTGs. Although practitioners were largely the same in both sectors, prescribing practices often differed dramatically. The extent of inappropriate prescribing in both sectors calls for in-depth investigation of the system factors and motivations that underlie problem practices, and the development of interventions that target these causative factors.