Effect of Five Alive fruit juice on the dissolution and absorption profiles of ciprofloxacin.

OBJECTIVE: To determine the effect of interaction of five Alive fruit juice on the dissolution and absorption profiles of ciprofloxacin tablets using urinary excretion. METHODS: In-vitro dissolution of ciprofloxacin 500 mg tablets was studied using US Pharmacopoeia dissolution apparatus II. This was conducted using 0.1N HCl and equal volumes of the fruit juice and 0.1N HCL. Samples were collected at predetermined time intervals for two hours. For the in-vivo study, eleven (5 males and 6 females) healthy volunteers participated in an open, single dose, cross-over randomized trial. After an overnight fasting, each volunteer either ingested a 500 mg ciprofloxacin tablet with 250 ml table water or with the fruit juice. Total urine voided was collected for 72 hrs after each dose of ciprofloxacin. Dissolution and urine samples were assayed using a controlled and validated UV spectrophotometric analysis. RESULTS: A lag time of 5 minutes was observed in dissolution profile of ciprofloxacin in the juice. The percent dissolved of ciprofloxacin in 0.1NHCl and fruit juice were found to be dissimilar (f2 =18.2) using similarity factor. There was statistical difference between the K(el) (elimination constant), K(e) (excretion rate) and X(u) (cumulative amount excreted unchanged) of subjects on water (0.1759 +/- 0.0144; 12.81 +/- 1.36; 375.5 +/- 41.2) and that of fruit juice (0.1250 +/- 0.0161; 7.6 +/- 1.07; 241.6 +/- 34.0). However, there was no difference between the t(1/2) of the subjects (4.2 +/- 0.3; 5.5 +/- 0.8). There was a decrease in relative availability of the drug by 35.75%. CONCLUSION: We conclude that the absorption of ciprofloxacin can be reduced by concomitant ingestion of the juice containing calcium carbonate and grape. Therefore to avoid drug therapeutic failures and subsequent bacterial resistance as a result of subtherapeutic level of the drug in the systemic circulation, ingestion of the juice with ciprofloxacin should be discouraged.

Survey of drug use practices and antibiotic prescribing pattern at a general hospital in Nigeria.

OBJECTIVE: To describe the current drug use practices at the institution, and gather baseline data, which can serve as a basis for designing an appropriate intervention to improve the drug use profile. METHOD: A retrospective audit of in- and out-patient prescriptions, generated during the period January-March 1999. Indicators of drug use pattern include: average number of drugs prescribed per encounter (ANDPE), average number of antibiotics prescribed per encounter (ANAPE), % encounter with antibiotics (PEA), percent of antibiotic prescriptions based on microbial sensitivity test results (MCST). Additionally, a "knowledge, attitude and practice" (KAP) survey of prescribers and dispensers was performed. Indicators of prescribing and dispensing quality include: sources of drug/prescribing information, availability and use of the hospital formulary, knowledge of the prescribing process and the adequacy of the drug supply management system. RESULTS: A total of 9984 outpatient prescriptions and 127 in-patient case notes were audited. The total number of prescribers and dispensers surveyed were 88 and 13 respectively. The ANDPE was found to be 3.16 for out-patients and 9.7 for in-patients, ANAPE was 1.1 and 2.4 for out-patients and inpatients respectively. The PEA was 50.3% for out-patients and 96.7% for in-patients. Only 4.2% of in-patient antibiotic prescriptions were based on MCST and percent encounter with switches in antimicrobial therapy was 52.1% while the average number of switches per encounter was 1.35. In 18.5% of the in-patient encounters there was evidence of drug incompatibilities. The KAP survey revealed that prescribers and dispensers in the hospital rely on different sources for their drug information needs (MIMS vs Martindale Extrapharmacoepia). None of the prescribers surveyed was able to correctly enumerate all the 4 steps involved in the prescribing process, about 25% got at least 2 steps correctly, and only 9.1% of the dispensers surveyed could accurately define a hospital formulary. The drug supply management system was found to be inadequate. CONCLUSION: The survey revealed that appreciable gaps in knowledge with respect to rational drug use, still exists among these cadre of healthcare professionals. The foregoing suggests an urgent need for review of current policies and systems in the hospital with the view of enhancing the drug use practices of the health providers. Specifically it is recommended that there should be an intervention program involving concerted continuing education (to influence the KAP of the various cadre of healthcare providers) and the establishment of a hospital formulary/standard treatment guidelines.

Open comparative randomised study of moclobemide versus amitriptyline in major depressive illness (DSM IIIR) in Nigeria.

In a multi-centre study, 60 patients (20 males and 40 females aged 43 +/- 15 and 37 +/- 15 years respectively) with a DSM-IIIR diagnosis of major depressive disorders were randomly assigned to treatment with either Moclobemide (maximum dose 600 mg per day) or Amitriptyline (maximum dose 150 mg per day) for eight weeks. Patients were evaluated pretreatment and over the 8 weeks treatment period using Hamilton Depression Rating Scale (HDRS) and the clinical global impressions (CGI). The Adverse Drug Effects Schedule, clinical, haematological and biochemical status were also evaluated pre, during and post treatment. Of the 60 patients enrolled for the study 54 were found evaluable for efficacy whilst all 60 were evaluated for safety (Adverse Event). On the HDRS and CGI scale there was no significant difference in the therapeutic outcome between the two treatment groups. In the overall clinical assessment rating at the end of treatment 94.1% of patients in the Moclobemide group were rated 'very good to good' and 94.4% with Amitriptyline. Moclobemide appeared to have a slightly better safety profile, the incidence of adverse event was 9.0% compared to 19.0% with Amitriptyline. The drop out rate was 16.7% and 26.7% for moclobemide and amitriptyline respectively. These differences were however not statistically significant. It was therefore concluded that moclobemide is an effective and safe alternative to amitriptyline, with attractive potential for out patients management of depressive illness.

Bioavailability of ciprofloxacin and fleroxacin: results of a preliminary investigation in healthy adult Nigerian male volunteers.

The absolute bioavailability (BA) of ciprofloxacin and fleroxacin were evaluated in 19 adult Nigerian male volunteers. Subjects meeting the selection criteria were randomized to receive treatment either with fleroxacin (200 mg-i.v. and 200 mg oral dose) or ciprofloxacin (200 mg-i.v. and 250 mg oral dose). The i.v./oral or oral/i.v. switch was made after a one week washout period. Blood and urine samples were collected at pre-determined time intervals over a 72 h period for analysis of drug levels. Following intravenous administration the maximum serum concentration (Cmax) was 2.7+/-1.06mg/l for ciprofioxacin and 0.99+/-0.41 mg/l for fleroxacin; the area under the blood level curve (AUC) was 8.82+/-3.19 mg x h/l with ciprofloxacin and 8.52+/-3.83 mg x h/l with fleroxacin. Following oral administration the Cmax was 1.52+/-0.94 mg/l with ciprofloxacin and 0.57+/-0.08 mg/l with fleroxacin; the AUC was 9.87+/-4.10 and 7.55+/-1.42 mg x h/l, respectively. The absolute BA following oral administration was found to be 0.79+/-0.47 for ciprofloxacin and 1.01+/-0.78 for fleroxacin. When these BA results were corrected for renal clearance [Cl(r)] and elimination half-life (t1/2) the values were reduced to 0.37+/-0.17 and 0.31+/-0.18, respectively, for ciprofloxacin and 0.53+/-0.23 and 0.99+/-0.38, respectively, for fleroxacin. Only 38% with ciprofloxacin and 59% with fieroxacin, of the administered dose, was excreted unchanged following oral administration. More work, however, needs to be done on ciprofloxacin to support and/or confirm the above findings. Fleroxacin, on the one hand, exhibited a different trend from that observed in the literature with respect to Cmax and AUC where the values observed in this study were 3--4 fold lower than expected following identical doses, whilst on the other hand the observed BA profile in this study was consistent with literature trends.

Interferon alfa-2a (Roferon-A) in the management of chronic hepatitis B infection: results of an open prospective study in Nigerian patients.

The efficacy and safety of recombinant interferon alfa-2a (rIFN) was evaluated in 26 adult Nigerian patients with chronic hepatitis B infection. Male and female patients with serological evidence of HBV infection (HBsAg and/or HBeAg positive patients) and abnormal liver histology were monitored for six months to confirm chronicity. At the end of the six months screening period eligible patient were enrolled into the study and treated with rIFN 4.5 MIU given three times a week for 6 months. Efficacy was assessed primarily by loss of HBV-DNA and/or HBeAg from serum and secondarily by loss of HBsAg and normalization of the liver histology. Safety was assessed by monitoring the leukocyte and platelet count over the treatment period whilst tolerability was assessed by recording the occurrence of adverse events (adverse drug reaction and intercurrent illness). At the end of therapy the response rate with respect to loss of HBV-DNA was 67% and 100% for HBeAg (i.e. for the six patients who were HBeAg positive at baseline). There was loss of HBsAg in 22.2% of the patients. A significant reduction in inflammation and necrosis scores was found among the 10 patients who had both baseline and term biopsies. The frequency of occurrence of adverse events was 53.8% and the laboratory safety parameters were not significantly affected by therapy (p > 0.05). 19.2% of the enrolled patients were withdrawn from the study prematurely. These results demonstrate that rIFN is effective in the management of CHB infection even in Nigerians. The high success rate associated with HBcAg clearance is particularly noteworthy.

Management of HIV infection in Nigeria with zalcitabine in combination with saquinavir mesylate: preliminary findings.

The efficacy and safety of a combination therapy with two anti-retroviral drugs, zalcitabine (ddC) and saquinavir mesylate was evaluated in 24 adult Nigerian patients with HIV infection. The result of an interim analysis after a 6-month course of therapy is presented herein. Patients were given zalcitabine 2.25 mg and saquinavir 1800 mg per day. Efficacy was evaluated by improvement in the CD4 cell count and disappearance and/or resolution of clinical signs and symptoms from the patient baseline condition. Tolerability and safety were assessed by the occurrence of adverse event and monitoring of biochemical parameters such as alanine transaminase, alkaline phosphatase and total bilirubin. The haemogram profile of patients was also monitored. There was clinical improvement in 79.2% of the patients, a minimal increase in the CD4 cell count was observed and the incidence of adverse event was 40%. The haematological and biochemical profile of the patients were not significantly affected by treatment (p > 0.05). We therefore conclude that the drug cocktail comprising zalcitabine and saquinavir does posses good potentials for effective management of Nigerian patients with HIV infection. However, it is imperative and important to continue treatment with the drugs for a longer time in order to demonstrate sustained response.

Interferon alfa-2a (Roferon-A) monotherapy in chronic myelogenous leukemia: a pilot study in Nigerian patients in early chronic phase.

The efficacy and safety of interferon alfa-2a monotherapy was evaluated in seventeen Nigeria patients with chronic myelogenous leukaemia (CML). Male and female patients with a mean age of 34.5 +/- 10.6 years were recruited into the study. Interferon therapy was administered at a maintenance dose of 9 MIU daily for 12 months. Efficacy was evaluated by assessing both haematologic and cytogenetic response, tolerability by incidence of adverse events and safety by laboratory haematological and biochemical indices. At the end of 12 months of therapy 6 patients (54.4%) had complete haematologic remission whilst 3 patients (100% of those evaluated) showed partial cytogenetic remission. The incidence of adverse event was 70% and the monitored haematologic and biochemical indices were not adversely affected by treatment. In conclusion, the study clearly demonstrated a significant benefit of interferon alpha-2a in the management of Nigerian patients with CML. The changes in the haematological and cytogenetic profiles between baseline and term were significant (p < 0.05). However, it is imperative and important to encourage and continue monitoring of the responding and stabilized patients beyond 12 months in order to demonstrate sustained response. The drug was reasonably well tolerated, however life threatening pancytopenia may pose a major problem in certain cases.

Treatment of malaria in north-eastern and south-eastern Nigeria: a population study of mefloquine, sulphadoxine, pyrimethamine combination (MSP) vs chloroquine (CQ).

In a population-based study involving 4019 patients in 20 peripheral health facilities in Nigeria, the outcome of presumptive malaria treatment with MSP was compared to that of CQ. The study was conducted between January 1995 and January 1996. Patients aged 6 months or more with a clinical diagnosis of malaria based on history of fever and axillary temperature > 37.5 degrees C were either treated with MSP (250 mg mefloquine, 500 mg sulphadoxine, and 25 mg pyrimethamine per tablet) or CQ (150 mg chloroquine base per tablet). The clinical cure rate was assessed by the disappearance of clinical signs and symptoms over a 7-day period. Tolerability was assessed by the incidence of adverse events (adverse drug reaction and intercurrent illness). The result shows that the clinical care rate of suspected malaria was 97.6% with MSP and 85.6% with CQ. The incidence of adverse event was 9.5% with MSP and 9.2% with CQ. The withdrawal rate was 2.0% with MSP and 5.0% with CQ; 3.5% of the patients in the CQ group withdrew due to adverse events compared to 0.47% with MSP. In conclusion it was observed that in addition to superior efficacy of MSP over CQ, fever clearance rate with MSP was comparable to that of CQ. The study also demonstrated that two tablets maximum dose of MSP is safe and effective in a large population of Nigeria malaria patients.

Efficacy and tolerability of a low-dose mefloquine-sulfadoxine-pyrimethamine combination compared with chloroquine in the treatment of acute malaria infection in a population with multiple drug-resistant Plasmodium falciparum.

The efficacy and tolerability of single, low-dose mefloquine, sulfadoxine-pyrimethamine (MSP) combination was compared with chloroquine (CQ) for malaria treatment in a malaria-endemic area of Nigeria with multiple drug-resistant Plasmodium falciparum. The two drug regimens (MSP and CQ) were tested in a 12-month prospective population study. The patients were divided into two groups. Group 1 patients were treated presumptively, based on malaria symptoms. Group 2 patients were treated based on a parasitologic diagnosis using the World Health Organization seven-day in vivo test and extended to a 28-day follow-up period. Tolerability was assessed by the incidence and intensity of adverse events. One thousand nine hundred thirty-five patients visiting 10 health facilities, including the University of Calabar Teaching Hospital, were enrolled. The study showed that the low-dose MSP was efficacious, with day 7 response rates of 95% and 91% for (presumptive) Group 1 and (in vivo) Group 2, respectively, while CQ had day 7 response rates of 82% and 66% in Groups 1 and 2, respectively. The low-dose MSP was significantly (P < 0.0001) more efficacious, with faster fever and parasite clearance times than CQ in this area of CQ-resistant P. falciparum malaria. Eight patients treated with CQ, including seven severe cases (RII-RIII) were successfully re-treated with MSP. Adverse events were generally more common among those treated with MSP (29%) than those treated with CQ (17%). However, the adverse events caused by both drugs were mild to moderate and self-limited. The MSP combination appears to be a good substitute for CQ, in view of multiple drug resistance, especially in areas with severe (RII-RIII) malaria.

Socio-economic implication of multi-drug resistant malaria in the community; how prepared is Nigeria for this emerging problem?

The control of faciparum malaria is becoming increasingly challenging in many endemic areas of the world, including Nigeria, due to the development of resistance to chloroquine and other anti-malarial drugs. Current rising health care costs demands that any preventive medicine and/or disease control program be judged according to its economic viability. As has been previously noted, any successful control of malaria will depend on socio-economic factors that influence its prevalence and management in the community. Cost-benefit or cost-effectiveness analysis of proposed and current intervention strategic are thus justified. This paper presents a review of studies involving socio-economic evaluation of the morbidity and mortality consequences of malaria. Studies involving health facility utilization profile for malaria in Nigeria and elsewhere are also reviewed. The review finds no studies evaluating or determining an appropriate economic model/framework for malaria control in Nigeria and concludes that as enormous and challenging the problem of multi-drug resistant malaria is, it can still be contained if control and management strategies are adopted based on sound and practical socio-economic judgement.

Comparative double blind study of the efficacy and safety of tenoxicam vs. piroxicam in osteoarthritis of knee and hip joints.

The efficacy and safety of tenoxicam was compared to that of piroxicam in 48 Nigerian patients with Osteoarthritis of the knee or hips. Of these 31 females and 11 males, with a mean age of 52.5 +/- 11.0 years, were evaluated for comparable efficacy and tolerability. On fulfilling the selection criteria each patient was treated with either tenoxicam 20 mg or piroxicam 20 mg daily for six weeks. Efficacy was evaluated in terms of presence of pain (at rest, with mobility and after one day of normal activity), functional status and physicians global assessment of therapeutic efficacy. Tolerability was evaluated by incidence of adverse events whilst safety was evaluated by measurement of haematological and biochemical profile pre and post therapy. Thirty seven patients had been on previous medication before being switched over to trial drug. There was a dose change in three patients in the piroxicam group due to inefficacy. Also there was loss of efficacy during maintenance in one patient in the piroxicam group. Clinical efficacy was judged excellent or good in 82.3% of patients with tenoxicam and 76.0% with piroxicam. Tolerability was excellent or good in 88.2% of patients with tenoxicam and 60.0% with piroxicam. The incidence of adverse event was 15.8% with tenoxicam and 21.7% with piroxicam. Overall, when judged on various evaluation parameters, tenoxicam 20 mg/day appears to be more effective and better tolerated than piroxicam 20 mg/day, though these differences were not statistically significant.

Single-dose pharmacokinetic study of ciprofloxacin and fleroxacin in healthy adult Nigerian volunteers.

The kinetics of absorption, distribution and elimination of ciprofloxacin and fleroxacin (following an intravenous dose of 200 mg), were evaluated in 24 adult healthy male Nigerian volunteers. Appropriate mathematical models were applied with the aid of a microcomputer software program for the estimation of the basic pharmacokinetic parameters. Appropriate statistical tests and profiles formed the basis for accepting or rejecting a proposed model. For parametric comparisons between the profile of the two drugs, the null hypothesis of no difference in their pharmacokinetic profile was proposed. All statistical tests were performed at a significance level of 95% (alpha = 0.05) and the 95% confidence level was determined where appropriate. Additionally, the model-independent or stochastic method of analysis was also employed in the pharmacokinetic evaluation of the blood level data. The parametric estimates obtained from both methods were compared. The plasma elimination half-life (t1/2) was estimated as 13.8 +/- 5.5 h for fleroxacin and 7.5 +/- 4.0 h for ciprofloxacin; the maximal plasma concentration (Cmax) was 0.8 +/- 0.3 and 2.3 +/- 1.0 mg/l for fleroxacin and ciprofloxacin, respectively, whilst the volume of distribution (Vd) was 2.5 +/- 1.6 and 0.4 +/- 0.3 liters/kg for fleroxacin and ciprofloxacin, respectively. 71 and 70% of unchanged drug were excreted in urine for fleroxacin and ciprofloxacin, respectively. With respect to comparative values, the results confirmed trends already observed in the literature, particularly as regards the t1/2. However, for fleroxacin there was a significant deviation from the literature trends with respect to Vd, Cmax and AUC. The results also confirmed earlier findings, advocating a once-daily dosage schedule for fleroxacin also in the Negroid population.

Fleroxacin vs Ciprofloxacin in the Management of Typhoid Fever: A Randomised, Open, Comparative Study in Nigerian Patients.

OBJECTIVE: The antibacterial efficacy of fleroxacin was compared with that of ciprofloxacin in 72 adult Nigerian patients with typhoid fever. PATIENTS AND METHODS: On inclusion into the study, patients were randomised to treatment with either fleroxacin 400mg once daily for 7 days or ciprofloxacin 500mg twice daily for 14 days. Clinical evaluations were performed on days 0, 1, 2, 3, 5 and 7 or 14, and 2 weeks after treatment. Bacteriology was performed on days 0, 3, 7 or 14, and 21 or 28. Laboratory tolerability parameters were monitored for all patients as well as incidence of adverse events. RESULTS: Bacteriological response on day 3 was 93.5 and 64.0% for fleroxacin and ciprofloxacin, respectively. At term and follow-up there was bacteriological cure in 97.0% of patients with fleroxacin and 100% with ciprofloxacin. The clinical cure was 100% for both groups at term. The incidence of adverse events was 5.4% with fleroxacin and 2.8% with ciprofloxacin. CONCLUSION: The results demonstrated that while the clinical response rate with both drugs was comparable, fleroxacin exhibited a faster bacteriological clearance rate. We therefore concluded that 7 days' therapy with fleroxacin 400mg once daily was as effective as 14 days' therapy with ciprofloxacin 500mg given twice daily in the management of typhoid fever in Nigerian patients. It was also observed that the quinolones possessed greater potential and benefits as first-line therapy for the management of typhoid fever in this environment. The tolerability profile was good for both treatment regimens.

Open comparative study of the efficacy, safety and tolerability of midazolam versus thiopental in induction and maintenance of anaesthesia.

In a multicentre study, 145 adult Nigerian patients presenting with diverse conditions (falling into ASA1 or ASA2 classification) for short surgical procedures (< 1 hour) were given either midazolam (0.15-0.20 mg/kg) or thiopentone (4-6 mg/kg) intravenously for induction of anaesthesia. Study population consisted of 58 male and 89 female patients with a mean age of 33.5 +/- 10.42 years. The primary efficacy criteria for induction of anaesthesia was induction time measured by the time of spontaneous closing of eyes and disappearance of palpebral reflexes following injection of trial drug. For maintenance of anaesthesia efficacy was assessed by the requirement of an additional dose of the anaesthetic agent either alone or in combination with other agents in addition to N20/O2 mixture. The secondary efficacy criteria was the degree of anterograde amnesia produced by trial drug, this was assessed by memory test. Safety was assessed by the frequency of the incidence of apnoea and cardio-stability measured by changes in the haemodynamic parameters (BP and pulse). Tolerability was evaluated by incidence of phlebitis or pain at the injection site. The standard efficacy population was all the 145 patients while only 100 patients were considered evaluable for maintenance efficacy. The mean induction time was 67.28 +/- 63.36 secs and 31.28 +/- 13.01 secs for the midazolam and thiopentone groups respectively. Anaesthesia was maintained with N20/O2 alone in 47% of patients in the midazolam group compared with 28.6% of patients in the thiopentone group. The degree of anterograde amnesia was significantly more pronounced in the midazolam group than in the thiopentone group (p = 0.000).(ABSTRACT TRUNCATED AT 250 WORDS)