The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration and in patients with chronic renal failure

The pharmacokinetics of orally administered ranitidine were studied in 10 patients with endoscopically proved duodenal ulceration after a single 150 mg dose and after 4 weeks 1 ranitidine treatment (150 mg twice daily), at which time there was endoscopic evidence of complete ulcer healing. After a single dose the median elimination half-life was 135 minutes and the median area under the curve (AUC) was l 844 ng/ml.hr. Although the maximum concentration after a single dose (Cmax = 365 ng/ml) was significantly different from that after continuous treatment (Cmax = 562 ng/ml) (p 65 ml/min). There appeared to be no significant differences in absorption rate or amount absorbed but the median elimination rate constant was significantly reduced from 0,31 h⁻¹ in controls to 0,14 h⁻¹ in RF (p <0,002) resulting in a two-fold increase in t½ (312 minutes) after a single dose. Cmax did not differ significantly although Cmin and AUC were significantly larger in RF patients (both p <0,002). It is suggested that the dosage of ranitidine be reduced from 150 mg to 75 mg twice daily in severe renal failure although it was not possible to relate half-life, elimination rate constant or AUC directly to creatinine clearance

A study of the relationship between the pharmacokinetics and the pharmacodynamics of atenolol in black and white subjects using an effect modelling technique.

Ph. D. University of Durban-Westville 1991.Abstract is available in PDF file

Intravenous and intramuscular magnesium sulphate regimens in severe pre-eclampsia

Patients with severe pre-eclampsia were randomised to receive magnesium sulphate according to an intramuscular (IM) (N =9) or an intravenous (IV) (N =8) regimen. The IM regimen consisted of a loading dose of 14 g (4 g IV and 10 g IM) followed by 5 g 4-hourly. Patients given the IV regimen received a 6 g IV loading dose followed by a maintenance infusion of 2 g/h. Clinical outcome, laboratory parameters and serum magnesium levels were recorded for both groups.There were no significant differences between groups with regard to clinical outcome of either mother or child. Similar average serum magnesium concentrations were produced by the regimens the only significant difference was that fluctuations in magnesium levels were greater with the IM than the IV regimen. None of the patients had seizures despite levels mostly below 2 mmol/l

The use of the SAEM algorithm in MONOLIX software for estimation of population pharmacokinetic-pharmacodynamic-viral dynamics parameters of maraviroc in asymptomatic HIV subjects

Using simulated viral load data for a given maraviroc monotherapy study design, the feasibility of different algorithms to perform parameter estimation for a pharmacokinetic-pharmacodynamic-viral dynamics (PKPD-VD) model was assessed. The assessed algorithms are the first-order conditional estimation method with interaction (FOCEI) implemented in NONMEM VI and the SAEM algorithm implemented in MONOLIX version 2.4. Simulated data were also used to test if an effect compartment and/or a lag time could be distinguished to describe an observed delay in onset of viral inhibition using SAEM. The preferred model was then used to describe the observed maraviroc monotherapy plasma concentration and viral load data using SAEM. In this last step, three modelling approaches were compared; (i) sequential PKPD-VD with fixed individual Empirical Bayesian Estimates (EBE) for PK, (ii) sequential PKPD-VD with fixed population PK parameters and including concentrations, and (iii) simultaneous PKPD-VD. Using FOCEI, many convergence problems (56%) were experienced with fitting the sequential PKPD-VD model to the simulated data. For the sequential modelling approach, SAEM (with default settings) took less time to generate population and individual estimates including diagnostics than with FOCEI without diagnostics. For the given maraviroc monotherapy sampling design, it was difficult to separate the viral dynamics system delay from a pharmacokinetic distributional delay or delay due to receptor binding and subsequent cellular signalling. The preferred model included a viral load lag time without inter-individual variability. Parameter estimates from the SAEM analysis of observed data were comparable among the three modelling approaches. For the sequential methods, computation time is approximately 25% less when fixing individual EBE of PK parameters with omission of the concentration data compared with fixed population PK parameters and retention of concentration data in the PD-VD estimation step. Computation times were similar for the sequential method with fixed population PK parameters and the simultaneous PKPD-VD modelling approach. The current analysis demonstrated that the SAEM algorithm in MONOLIX is useful for fitting complex mechanistic models requiring multiple differential equations. The SAEM algorithm allowed simultaneous estimation of PKPD and viral dynamics parameters, as well as investigation of different model sub-components during the model building process. This was not possible with the FOCEI method (NONMEM version VI or below). SAEM provides a more feasible alternative to FOCEI when facing lengthy computation times and convergence problems with complex models

Does osteoporosis predispose falls? a study on obstacle avoidance and balance confidence

Contains fulltext : 96832.pdf (publisher's version ) (Open Access)BACKGROUND: Osteoporosis is associated with changes in balance and physical performance and has psychosocial consequences which increase the risk of falling. Most falls occur during walking; therefore an efficient obstacle avoidance performance might contribute to a reduction in fall risk. Since it was shown that persons with osteoporosis are unstable during obstacle crossing it was hypothesized that they more frequently hit obstacles, specifically under challenging conditions. METHODS: Obstacle avoidance performance was measured on a treadmill and compared between persons with osteoporosis (n = 85) and the comparison group (n = 99). The obstacle was released at different available response times (ART) to create different levels of difficulty by increasing time pressure. Furthermore, balance confidence, measured with the short ABC-questionnaire, was compared between the groups. RESULTS: No differences were found between the groups in success rates on the obstacle avoidance task (p = 0.173). Furthermore, the persons with osteoporosis had similar levels of balance confidence as the comparison group (p = 0.091). The level of balance confidence was not associated with the performance on the obstacle avoidance task (p = 0.145). CONCLUSION: Obstacle avoidance abilities were not impaired in persons with osteoporosis and they did not experience less balance confidence than the comparison group. These findings imply that persons with osteoporosis do not have an additional risk of falling because of poorer obstacle avoidance abilities

Counting the costs: Comparing depot medroxyprogesterone acetate and norethisterone oenanthate utilisation patterns in South Africa

BACKGROUND: In South Africa, where health care resources are limited, it is important to ensure that drugs provision and use is rational. The Essential Drug List includes depot medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-EN) as injectable progestagen-only contraceptives (IPCs), and both products are extensively used. OBJECTIVES AND METHODS: Utilisation patterns of the injectable contraceptive products DMPA and NET-EN are compared in the context of current knowledge of the safety and efficacy of these agents. Utilisation patterns were analysed by means of a Pareto (ABC) analysis of IPCs issued from 4 South African provincial pharmaceutical depots over 3 financial years. A case study from rural KwaZulu-Natal, South Africa, is used to examine utilisation patterns and self-reported side effects experienced by 187 women using IPCs. RESULTS: IPCs accounted for a substantial share of total state expenditure on drugs. While more DMPA than NET-EN was issued, NET-EN distribution from 2 depots increased over the 3-year period. Since DMPA was cheaper, if all NET-EN clients in the 1999/2000 financial year (annualised) had used DMPA, the 4 depots could have saved 4.95 million South African Rands on product acquisition costs alone. The KZN case study showed slightly more NET-EN (54%) than DMPA (46%) use; no significant differences in self-reported side effects; and that younger women were more likely to use NET-EN than DMPA (p = 0.0001). CONCLUSIONS: Providing IPCs on the basis of age is not appropriate or cost effective. Rational use of these products should include consideration of the cost of prescribing one over another

Where is the Condom? Contraceptive Practice in a Rural District of South Africa

Interviews were conducted with 848 African women aged 1549 years in a rural area of South Africa to determine the extent to which condoms are used, reasons for contraceptive method choice and unmet contraceptive need. Injectable contraceptives were being used by 22.1% of respondents, who considered them to be convenient, safe, effective, and/or a method that could be used secretly. The decision to use this method was often made on the recommendation of a health worker. Eleven women said they were using the male condom, seven of whom were using it because it provides protection against pregnancy and sexually transmitted infections. Many (70.3%) women were not using any form of contraception. Counselling about contraceptive options should take into account the need for dual protection, and strategies for increasing condom use should be promoted. (Afr J Reprod Health 2002; 6[2]: 7178) Résumé Où est le préservatif? Lusage du contraceptif dans un district rural de lAfrique du Sud. Nous avons eu des entretiens avec 848 femmes africaines âgées de 1549 ans dans une région rurale de lAfrique du Sud pour déterminer lampleur de lusage des préservatifs, la raison pour le choix de la méthode contraceptive et le besoin de contraceptif qui na pas été satisfait. 22,1% des répondantes utilisaient des contraceptifs injectables quelles considéraient comme étant convenables, saufs, efficaces et/ou comme une méthode quon pouvait utiliser en cachette. Cétait sur la recommendation dune assistante sociale que la décision demployer cette méthode a été souvent prise. Onze femmes ont déclaré quelles utilisaient le préservatif pour hommes; 7 dentre elles lutilisaient parce quil sert de protection contre la grossesse et les infections sexuellement transmissibles. Beaucoup de femmes (70,3%) nutilisaient point de contraception. It faut que les conseils sur les options contraceptives tiennent compte de la nécessité pour la double protection; il faut également promouvoir les stratégies pour laugmentation de lusage du préservatif. (Rev Afr Santé Reprod 2002; 6[2]: 7178) Key words: Contraception, condoms, dual protection, South Afric

Dual Protection against Sexually Transmitted Infections and Pregnancy in South Africa

Promotion of simultaneous protection against sexually transmitted infections (STIs) and unintended pregnancy, referred to as dual protection, represents an important public health intervention. We investigated its prevalence and correlates in South Africa. A cross-sectional survey of 929 sexually active women, aged 15-49 years, was conducted in 89 public primary health care clinics, with dual method use and use of condom alone at last sexual intercourse as outcomes. At last intercourse, 12% of women were protected from both STIs and pregnancy. In multivariate analysis, higher education, being unmarried, and multiple sex partnership in the past year were predictors of dual method use, while younger age, higher education and awareness of the dual function of condoms were predictors of condom use alone. Dual protection is low in this population. The predominance of hormonal contraceptive use in South Africa means that increasing barrier method use among hormonal contraceptive users is an important strategy for increasing dual protection. (Afr J Reprod Health 2003; 7[2]: 13-19