Browsing by Author "Madsen, Richard"

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    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.
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    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.
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    Socio-economic status and menarcheal age in urban african schoolgirls in the western cape, South Africa
    (University of Stellenbosch, 2008) Travill, Andre L.; Madsen, Richard; Cameron, Noel; Kemper, Han C.
    The impact of different socio-economic levels, height, weight and sum of four skinfolds on the menarcheal age of 302 Black, South African school girls ranging in age from 8 to 17 years was researched. Socioeconomic status was obtained by means of a questionnaire that focused on the education, income, and occupations of the parents of the participants and the accommodation in which they were reared. Menarcheal age was obtained by means of a questionnaire. When restricted to those girls who had reached menarche, the mean age was found to be 14.34 years (SD=0.93). The application of survival analysis revealed an estimated median age of 14.25 years with a 95% confidence interval estimate of 14.08 and 14.58. Based on the log-rank statistic, significant differences were found in the survival curves of the different SES categories (p=0.0098). It was found that lower SES corresponded to curves having longer survival times, i.e. later ages of menarche. Differences were found in weight (p=0.037) and in height (p=0.0042), but no difference in SUM4 (p=0.44), between girls who have reached menarche and those who have not.