Prof. Pierre Mugabo

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https://hdl.handle.net/10566/2047

Position:	Professor of Pharmacology
Department:	The School of Pharmacy
Faculty:	Faculty of Natural Science
Qualifications:	MBChB (Rwanda), MMed Cardiology (Louvain) , PhD Pharmacology (Ghent)
	Research publications in this repository
More about me:	here and here
Tel:	021 959 3441
Fax:	021 959 3407
Email:	pmugabo@uwc.ac.za

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Now showing 1 - 14 of 14

Do HIV infection and antiretroviral therapy influence multidrug-resistant tuberculosis treatment outcomes?
(Academic Journals, 2015) Mugabo, Pierre; Adewumi, A.O.; Theron, Danie; Burger, Andries; Van, Zyl L.
The aim of this study was to find out whether human immunodeficiency virus (HIV)-infection and antiretroviral drugs influence multidrug-resistant (MDR)-tuberculosis (TB) treatment outcomes. The study compares MDR-TB treatment outcomes between HIV-positive and HIV-negative patients. It involved patients admitted for treatment of MDR-TB between 1 January 2004 and 31 December 2006. From 363 patients selected, 268 (177 males and 91 females) had MDR-TB and 95 patients (59 males and 36 females) were co-infected with HIV. Children in the HIV-negative group were 41 and 7 in the HIV-positive group. The HIV-infection was treated with Stavudine, Lamivudine and Efavirenz in 54 patients. Kanamycin, Ethionamide, Ofloxacin, Terizidone, Pyrazinamide and Ethambutol were used for MDR-TB treatment. In HIV-negative and HIV-positive patients MDR-TB treatment outcomes were, respectively as follows: 37 and 35% cure, 9 and 5% treatment failure, 20 and 25% lost to follow up, 11 and 17% mortality, 19 and 13% treatment completed, 6 and 5% transfer-out. The cure rate was 100% in children. In HIV-positive patients, MDR-TB cure rate was 35% in patients on ARVs and 34% in patients not receiving ARVs. The difference between these cure rates is not statistically significant (p-value = 0.79). The median (range) duration of ART before the start of MDR-TB treatment was 10.5 (1 to 60) months and did not influence MDR-TB treatment outcomes. In children, the full treatment was supervised in hospital. This could explain the 100% cure rate. Adults' treatment was supervised in hospital only during the intensive phase then followed up as out patients over 18 months. According to the results of this study, HIV-infection and antiretroviral therapy did not influence MDR-TB treatment outcomes.
Acute pharmacokinetics of first line anti-tuberculosis drugs in patients with Pulmonary Tuberculosis and in patients with Pulmonary Tuberculosis co-infected with HIV
(David Publishing, 2011) Mugabo, Pierre; Hassan, Mogamat Shafick; Slaughter, R.
The aim of this study was to compare the pharmacokinetics of antituberculosis drugs in patients with pulmonary tuberculosis (PTB) and in patients with PTB and HIV during the first 24 h of treatment. Designed as a case-control study, it compares the pharmacokinetics of first line antituberculous drugs, in HIV-positive (cases) and HIV-negative (control) patients both presenting with pulmonary tuberculosis. Blood samples were collected before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 8, 12 and 24 h after administration of drugs. Drugs plasma levels were tested using HPLC assays. Results: Fourteen HIV positive (7 males and 7 females) and 17 HIV negative (9 males and 8 females) enrolled. Rifafour, a combination tablet including rifampicin, isoniazid, pyrazinamide and ethambutol was used in HIV positive patients, CD4 counts were significantly lower, renal function mildly decreased in 85% patients and moderately decreased in 7% patients. Liver function was normal in both groups. None of these patients was on other drug therapy. In the HIV positive group isoniazid T1/2 and AUC were decreased and Cl increased whereas Tmax and Cmax were unchanged. Pyrazinamide Tmax and Cmax were significantly decreased in HIV positive patients and no significant changes were noticed in the T1/2, AUC and CL. Conclusion: The study suggest that ethambutol, pyrazinamide and rifampicin pharmacokinetics was not affected by HIV infection and that isoniazid disposition is affected by HIV.
Potential beneficial effects of Tulbaghia violacea William Henry Harvey (Alliaceae) on cardiovascular system - A review
(Pharmacotherapy Group, University of Benin, 2015) Ismaila, Raji; Kenechukwu, Obikeze; Mugabo, Pierre
Tulbaghia violacea William Henry Harvey (Harv. Alliaceae) is a small bulbous herb belonging to the family Alliaceae. It is used in South Africa to treat fever, colds, asthma, paralysis, and hypertension. Meanwhile, cardiovascular disease accounts for about 30 % of total global death, with most of these deaths occurring in low and middle-income countries. Furthermore, people in low-income countries are still largely dependent on plants in their surroundings for both prophylaxis and treatment of diseases, partly due to limited access to and cost of pharmaceuticals, and folkloric evidence of the potency of medicinal plants and/or local belief systems. Therefore, the present review aims to proffer possible ways by which T. violacea may improve cardiovascular outcomes. An extensive and systematic review of the literature was carried out, and relevant findings presented in this review. There is evidence that T. violacea may modulate the renin-angiotensin system, the autonomic nervous system, oxidative stress and haemostasis, with resultant protection of the cardiovascular system in both health and disease.
Determination of kanamycin plasma levels using LC-MS and its pharmacokinetics in patients with multidrug-resistant tuberculosis with and without HIV-infection
(OMICS, 2015) Mugabo, Pierre; Abaniwonda, Mercy, I.; Theron, Danie; Hassan, Shafick, M.; Stander, Marietjie; Van Zyl, Leonie; McIlleron, Helen; Madsen, Richard
The objectives of the study were: (1) to determine kanamycin plasma concentrations using liquid chromatography coupled with mass spectrometry (LC-MS), (2) to investigate kanamycin pharmacokinetics (PK) in patients with multi-drug resistant tuberculosis (MDR-TB), (3) to find out whether HIV infection, kidney dysfunction and antiretroviral drugs influence kanamycin PK. The study was designed as a non-randomized study involving male and female HIV- positive and HIVnegative patients admitted for MDR-TB treatment. Blood samples were collected before (baseline) and ½, 1, 2, 4, 8 and 24 hours after intramuscular injection of kanamycin. LC-MS was used to quantify kanamycin plasma concentrations. Thirty one patients including 13 HIV (+) participated in the study. The lower limit of detection and lower limit of quantification of kanamycin were 0.06 μg/ml and 0.15 μg/ml respectively. Kanamycin PK parameters were described and there was no significant difference between HIV-positive and HIV-negative patients. A statistical significant difference (p=0.0126) was found in the renal function in HIV - positive and HIV - negative patients. However, this difference did not affect kanamycin elimination. No interactions have been identified between antiretroviral drugs and kanamycin. Conclusion: LC-MS analysis method is highly specific and highly sensitive in the detection and quantification of kanamycin plasma concentrations. Kanamycin PK in patients with MDR-TB was described. Due to a limited number of patients, we cannot rule out any influence of HIV - infection, renal impairment and antiretroviral drugs on kanamycin pharmacokinetics. The relationship between the area under the curve of kanamycin free plasma concentrations (fAUC) and its minimum inhibitory concentrations (MIC) on M.tuberculosis isolated from the sputum of each patient should be assessed. Therefore, kanamycin free plasma concentrations and MIC should be determined.
Iterative prophylactic treatment by hematin in two cases of recurrent disabling acute intern1ittent porphyria (AIP)
(Elsevier, 1989) Mugabo, Pierre; Coche, Lefebvre E.; Hassoun, A.
Summary: Hematin is known as a useful drug in the treatment of acute intermittent porphyria (Al P) attacks. We have used it with success as an iterative prophylactic treatment in two cases of AIP with recurrent disabling crises. In one of the two cases, the kinetic study of plasmatic delta amino-fernlinic acid (ALA) has shown an ALA plasma level (40-45 μg/dl) which is considered to be a trigger level for this patient. Cntil now, no side effects due to such a hematin treatment have been observed in either patient. This schedule could represent an improvement in the management of recurrent disabling AI P crises.
Active Principles of Tetradenia riparia; II. Antispasmodic Activity of 8(14), 15-Sandaracopimaradiene-7α, 18-diol
(Georg Thieme Verlag, 1987) Van Puyvelde, Luc; Lefebvre, Romain; Mugabo, Pierre; De Kimpe, Norbert; Schamp, Niceas
Tetradenia riparia is one of the most popular medicinal plants in Rwanda. Previously, several new substances have been isolated from the leaves, including a new diterpenediol, i.e. 8(14),15-sandaracopimaradiene-7α,18-diol. This new diterpenediol exhibits a papaverine-like antispasmodic activity on the contractions of the guinea pig ileum provoked by methacholine, histamine, and barium chloride and on the noradrenaline-induced contractions of the rabbit aorta.
Effects of aqueous leaf extract of Asystasia gangetica on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats
(BioMed Central Ltd, 2013) Mugabo, Pierre; Raji, Ismaila A.
Background: Asystasia gangentica (A. gangetica) belongs to the family Acanthaceae. It is used to treat hypertension, rheumatism, asthma, diabetes mellitus, and as an anthelmintic in South Africa, India, Cameroun, Nigeria, and Kenya respectively. It has also been reported to inhibit the angiotensin I converting enzyme (ACE) in-vitro. Therefore, the aim of this study is to investigate the in-vivo effect of aqueous leaf extract (ALE) of A. gangetica on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats (SHR); and to elucidate possible mechanism(s) by which it acts. Methods: The ALE of A. gangetica (10–400 mg/kg), angiotensin I human acetate salt hydrate (ANG I, 3.1–100 μg/kg) and angiotensin II human (ANG II, 3.1–50 μg/kg) were administered intravenously. The BP and HR were measured via a pressure transducer connecting the femoral artery to a Powerlab and a computer for recording. Results: A. gangetica significantly (p<0.05), and dose-dependently reduced the systolic, diastolic, and mean arterial BP. The significant (p<0.05) reductions in HR were not dose-dependent. Both ANG I and ANG II increased the BP dose-dependently. Co-infusion of A. gangetica (200 mg/kg) with either ANG I or ANG II significantly (p<0.05) suppressed the hypertensive effect of both ANG I and ANG II respectively, and was associated with reductions in HR. Conclusions: A. gangetica ALE reduced BP and HR in the SHR. The reduction in BP may be a result of actions of the ALE on the ACE, the ANG II receptors and the heart rate.
Characterization and Cradiovascular Effects of (13S)-9α,13α-epoxylabda-6β(19),15(14)diol dilactone, a Diterpenoid Isolated from Leonotis leonurus
(South African Chemical Institute, 2008) Obikezea, Kene C.; McKenzieb, Jean M.; Green, Ivan; Mugabo, Pierre
A new diterpenoid, (13S)-9 ,13 -epoxylabda-6 (19),15(14)diol dilactone (1), was isolated from Leonotis leonurus and the structure determined via NMR analysis. The compound causes significant changes in blood pressure of anaesthetized normotensive rats and exhibits a negative chronotropic effect.
Nevirapine plasma concentrations in premature infants exposed to single-dose nevirapine for prevention of mother-tochild transmission of HIV-1
(Health and Medical Publishing Group, 2011) Mugabo, Pierre; Els, Ilse; Smith, Johan; Rabie, Helena; Smith, Peter; Mirochnick, Mark; Steyn, Wilhelm; Hall, David; Madsen, Richard; Cotton, Mark F.
Background: No pharmacokinetic data exist for premature infants receiving single-dose nevirapine (sd NVP) for prevention of mother-to-child transmission (MTCT) of HIV. Aim: To describe NVP decay pharmacokinetics in two groups of premature infants – those whose mothers either received or did not receive NVP during labour. Methods: Infants less than 37 weeks’ gestation were prospectively enrolled. Mothers received sd NVP during labour if time allowed. Infants received sd NVP and zidovudine. Blood was collected on specified days after birth and NVP concentrations were determined by liquid chromatography-mass spectrometry. Results: Data were obtained from 81 infants, 58 born to mothers who received sd NVP during labour (group I) and 23 to mothers who did not receive NVP (group II). Of the infants 29.6% were small for gestational age (SGA). Median (range) maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under the plasma concentration-time curve (AUC) and halflife (T½) were 1 438 (350 - 3 832) ng/ml, 25h50 (9h40 - 83h45), 174 134 (22 308 - 546 408) ng×h/ml and 59.0 (15.4 - 532.6) hours for group I and 1 535 (635 - 4 218) ng/ml, 17h35 (7h40 - 29h), 168 576 (20 268 - 476 712) ng×h/ml and 69.0 (22.12 - 172.3) hours for group II. For group II, the median (range) volume of distribution (Vd) and body clearance (Cl) were 1 702.6 (623.7 - 6 189.8) ml and 34.9 (6.2 - 163.8) ml/h. The AUC was higher (p=0.006) and Cl lower (p<0.0001) in SGA infants. Plasma concentrations exceeding 100 ng/ml were achieved over 8 days in 78% infants in group I and 70.0% in group II. The MTCT rate was 4.8%. Conclusion: Women in preterm labour often deliver with little advance warning. Our study suggests that NVP dosing of preterm infants as soon as possible after birth without maternal intrapartum dosing may be as effective as combined maternal and infant dosing.
Provision of syndromic treatment of sexually transmitted infections by community pharmacists: a potentially underutilized HIV prevention strategy
(Lippincott, Williams & Wilkins, 2003) Ward, Kim; Butler, Nadine; Mugabo, Pierre; Klausner, Jeffrey; Mcfarland, Willi; Chen, Sanny; Schwarcz, Sandra
Background: Sexually transmitted infections (STIs) are known risk factors for HIV infection. Goal: The goal of this study was to assess the current and potential future role that community pharmacists in Western Cape, South Africa play in the treatment of STIs. Study Design: A cross-sectional survey of community pharmacists in the Western Cape region of South Africa. A face-to-face interview that ascertained experience with requests from patients for STI treatment, current STI treatment practices, and willingness to provide syndromic STI treatment was administered to head pharmacists. Results: Ninety pharmacies were selected and 85 (94%) of the head pharmacists participated; 55 from an urban area and 30 from a rural area. Pharmacists reported a median of 40 urban clients and 25 rural clients who sought STI treatment from community pharmacists. When provided with a hypothetical clinical situation, 13% of urban and 17% of rural pharmacists identified the correct medication for male urethral discharge, 8% of urban pharmacists and none of the rural pharmacists identified correct treatment for genital ulcers, and none of the pharmacists identified the correct medication for vaginal discharge. Fifty-three percent of pharmacists in urban regions and 47% of pharmacists in rural regions expressed willingness to provide syndromic STI treatment. Independent predictors of willingness to provide syndromic treatment were knowledge of the link between HIV transmission and STIs (adjusted odds ratio [OR]: 13.78; 95% CI: 2.69,70.66), past experience prescribing syndromic STI treatment (OR: 11.1; 95% CI: 1.14, 108.6), and male gender (OR: 4.38; 95% CI: 1.15, 16.7). Conclusions: Pharmacists are frequently called upon to provide STI treatment but have limited knowledge of correct treatment recommendations. Training pharmacists to provide syndromic STI treatment may be one strategy to reduce STI morbidity and HIV transmission.
Inorganic ions in leonotis leonurus extract do not explain changes in isolated Wistar rat heart function
(Open Access Science Research Publisher, 2011) Burger, Andries; Mugabo, Pierre; Henkel, Ralf; Green, Ivan
Leonotis leonurus (L. leonurus) R. Br (Lamiaceae) is used by healers in South Africa. The present study was conducted to determine if the L. leonurus effect on isolated rat heart is due to ionic changes in the perfusion fluid.
The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea
(BioMed Central, 2013) Raji, Ismaila A.; Mugabo, Pierre; Obikeze, Kenechukwu
Background: Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma aldosterone levels to its anti-hypertensive effect. Methods: In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30–120 mg/kg), muscarine (0.16 -10 μg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS)) were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR) weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 μg/kg) was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments, the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea (60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the chronic experiment. Results: In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with T. violacea; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violaceatreated and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the captopril-treated group; while no difference in HR was observed among the groups. Conclusion: The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea.
Cardiovascular effects of the alkaloid hippadine on the isolated perfused rat heart
(Open Access Science Research Publisher, 2012) Mugabo, Pierre; Obikeze, Kenechukwu; Njagi, Angela; Burger, Andries; Dietrich, Danielle; Green, Ivan
Crinum macowanii has been used extensively in traditional medicines for treatment of various illnesses such as oedema and ‘heart disease’. Previous studies of the crude bulb extracts on Langendorff perfused isolated rat hearts indicated a positive inotropic effect. The aim of this study was to isolate and characterize compound(s) from C. macowanii with cardiovascular effects similar to that observed with the crude extracts of the plant. The methanol extract of dried bulbs was extracted for alkaloids, and structural elucidation of the isolated alkaloid identified it as hippadine. The cardiovascular effects of hippadine was evaluated in vitro in isolated perfused rat hearts using the “double sided” working heart system. Perfusion with 0.5 μg/ml and 5.0 μg/ml hippadine in Krebs-Hanseleit buffer led to significant decreases in coronary flow, aortic output, cardiac output, systolic pressure, and heart rate, accompanied by increases in diastolic pressure. Hippadine exhibited a negative chronotropic and inotropic effect on the isolated rat heart and is responsible either partly or fully for the cardiovascular effects of C. macowanii.
Effects of Leonotis leonurus aqueous extract on the isolated perfused rat heart
(Open Access Science Research Publisher, 2012) Mugabo, Pierre; Khan, Fatima; Burger, Andries
The use the aqueous decoction of Leonotis leonurus (L. leonurus) (Ll) R. Br. (Lamiaceae) in the treatment of hypertension (HPT) in traditional medicine is well documented. The effect of the aqueous extract of LI on the blood pressure (BP) and heart rate (HR) has been investigated in normotensive rats. The aim of this study was to investigate the effect of Ll aqueous extract on the in isolated perfused rat heart (IPRH). Hearts were excised from male Wistar albino rats weighing 250-350g, aged less than 6 months. They were perfused at constant flow using the modified Langendorff perfused model of the heart. Effects of adrenaline on the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), heart rate (HR), cardiac work (CW) and coronary perfusion pressure (CPP) were compared to that of Ll. Adrenaline (1µM) significantly (p<0.05) increased the LVSP by 40.6%, the LVDP by 43.9%, the HR by 22.5% and the CW by 89.4%. Ll (1.0 mg/ml and 2.0 mg/ml respectively and significantly (p<0.01) increased the LVSP by 25.36 and 14.91, the LVDP by 29.40 and 14.88. Ll (1.0 mg/ml and 2.0 mg/ml) significantly produced a negative chronotropic effect. Both adrenaline and Ll aqueous extract did not have any significant effect on the LVEDP. Adrenaline resulted in positive inotropic and chronotropic effects. At low concentrations Ll produced a positive inotropic and a negative chronotropic effect. At the concentration of 2.0mg/ml Ll decreased all parameters to zero. At higher concentrations higher than 2.0mg/ml, Ll seemed to have toxic effects on the heart.

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