Residues of organochlorine pesticides in human milk

A research paper on residue of pesticides in human milk.Levels of residues of chlorinated hydrocarbons p,p-DDT, p,p-DDE, p,p-TDE, x-, B-, y-hexachlorocyclohexane (HCH), heptachlor epoxide, dieldrin and polychlorinated biphenyls (PCBs) in the milk of 40 Zimbabwean mothers living in the Greater Harare area were analysed. Of all the milk samples analysed, relatively low residue levels of x-, B-, and v-HCH, peptochloroperoxide and dieldrin were detected in 58, 100, 63, 13 (not statistically significant) and 65 per cent respectively. Traces of the PCB congener 2,2,4,5,5 -penta- chlobipheny (PCB 101) were found in 15 samples. One sample contained traces of 2,3',4,4',5-pentachlorobiphenyl (PCB 118). From this study, small though the sample was, it seems social status, educational background and living conditions are important demographic variables influencing the frequency distribution of residue levels of sum DDT in the mother’s milk

Epidemiology of the health impact of pesticide use in Zimbabwe

A study of the implications of pesticide exposure to Zimbabwe's occupational health regulations.About 30-50 per cent of the workers on large-scale commercial farms involved in pesticide use in Zimbabwe are exposed to organophosphates during the spraying season. Pesticide exposure is associated with use of manual techniques, little provision of protective clothing and inadequate safety information. There is evidence that pesticide exposure spills over into non-spravers and into the communities living on farms. Hospital admissions for acute poisoning appeal' to be a poor guide to the extent of sub-acute or chronic exposure to pesticides, given the extent of exposure documented in the surveys. The use of simple biological monitoring techniques can be extremely useful in epidemiological assessment of patterns and possible sources of exposure. The findings of the studies reported in this chapter add weight to the growing body of evidence that there is a need for a greater allocation of resources towards identifying and controlling the negative health impact of pesticide use in developing countries

Metabolism of pesticides

A research paper on how pesticides infiltrate the biological systems of living organisms.The metabolism of pesticides, like that of many other chemicals, takes place mainly in the liver, skin, gastrointestinal tract, kidneys and lungs. These organs have the capacity to bring about enzymatic reactions of metabolism. In this chapter, metabolism of pesticides is exemplified by the metabolic pathways of the organochlorine, DDT, and the organophosphate, parathion. Metabolism means more than just one thing. On one hand, the chemical and enzymatic reactions and processes that maintain the existence of any organism may be referred to as metabolism. On the other hand, metabolism may mean the conversion or transformation of chemical substances foreign and endogenous to an organism by chemical or enzymatic reactions in the organism. “Foreign compounds" refers to non-nutrient substances to a specific organism. Pesticides may enter the body by way of ingestion in food or drink, inhalation, through the eyes or by absorption through the skin (Neal, 1975). The metabolism of pesticides, that is, the total fate of pesticides in the body, including their absorption, distribution, biotransformation and excretion like that of other foreign substances is handled in the body by certain organs. Although the liver is perhaps the major organ involved in metabolism of chemicals, the kidney, skin, the gastrointestinal tract (GIT) and the lungs are all involved in metabolism too (Briggs and Briggs, 1974). A more detailed account of the mechanisms of metabolism is presented by Williams (1959) and La du et al. (1971)

Technological and cost comparison of cytochrome P450 2B6 (516G>T) genotyping methods in routine clinical practice

Pharmacogenetics requires robust and affordable tests to determine genetic variability. This study compares three genotyping methods: gene re-sequencing, real time polymerase chain reaction (PCR) allelic discrimination and PCR-RFLP for the detection of a genetic variation (516G>T) in the gene which codes for the enzyme, CYP2B6, the main enzyme in the metabolic pathway of the antiretroviral drug, efavirenz. The CYP2B6 (516G>T) variant has reduced metabolic capacity. Twenty (20) samples obtained from human immunodeficiency virus acquired immunodeficiency syndrome (HIV/AIDS) positive patients on an efavirenz containing regimen were used to establish whether these methods produce the same CYP2B6 genotype results on the same samples. Results were directly compared for concordance and revealed a 100% correlation with all three methods. Comparison for cost of equipment and reagents required for each method revealed an order of: sequencing > real time-PCR > PCR-RFLP. This study demonstrates the reproducibility of these three methods and provides an opportunity for the clinical applicability in routine clinical practice.Keywords: Polymorphism, drug response, efavirenz, Zimbabwe.African Journal of Biotechnology Vol. 12(19), pp. 2706-271

Occupational exposure to DDT among the mosquito-control sprayers in Zimbabwe

A research paper on occupational health problems in the seasonal spraying business due to DDT exposure in Zimbabwe.Four hundred and eighty DDT seasonal spray-men were screened for DDT exposure over the period September to March in 1988, 1989 and 1990. The average age of the spray-men was 29 ± 8,5 (range 19-61 years). Their average weight was 62,8 ± 4,7 kg with a range of 44-129 kg. Ninety per cent of the men were between the age of 21 and 50 years. Up to 49 per cent of the spray-men showed evidence of DDT exposure with DDE plasma levels greater than 1,00 pg per 100 ml and vitamin A levels greater than 0,92 mg per litre. Smoking seems to predispose the workers to toxic exposure with 76 per cent of the smokers showing vitamin A levels above normal compared to 58 per cent non- smokers. Forty-eight percent of the men were on medication during the spraying period, the significance of which was not evaluated in this study. The study indicated an unacceptably high magnitude of toxic exposure to DDT among spray-men

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study

Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration–time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (Cmax) and concentration at 12 h (C12h) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs). Pharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00–1.14) for the AUC; 1.06 (0.98–1.16) for Cmax and 1.03 (0.92–1.16) for C12h. Co-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine. Trial registration number NCT01410058 (ClinicalTrials.gov

CYP2D6*17 polymorphism and tardive dyskinesia in black psychotic patients on typical antipsychotics

Background: Tardive dyskinesia is a debilitating, intractable, hyperkinetic movement disorder which contributes to an increase in psychiatric morbidity. Reduced function CYP2D6 alleles have been associated with tardive dyskinesia pathogenesis amongst Caucasians and Asians, with CYP2D*4 and *6 and CYP2D6*10 being implicated in these races respectively. No similar study has been successfully conducted in black Africans. Objective: To determine the relationship between tardive dyskinesia and CYP2D6*17 (the major reduced function CYP2D6 allele in Africans). Methodology: Abnormal Involuntary Movements Scale (AIMS) scoring and CYP2D6 genotyping were carried out on psychiatric patients exposed to typical antipsychotic medications in an unmatched case control study. A case of tardive dyskinesia was defined as a patient with an AIMS score ≥ 2 in two body areas OR ≥ 3 in one body area Results: A total of 18 cases and 32 controls made up the study sample.The sample’s mean age was 36.9±12.0 years with median treatment duration of 7.0 years (range: 0.25 to 38 years). Multiple logistic regression revealed no significant association between tardive dyskinesia and CYP2D6*17 (OR=0.252; 95% CI: 0.038 to 1.647; p=0.150). However, use of chlorpromazine (OR=5.754; 95% CI: 1.024 to 32.328; p=0.047) and age at treatment initiation (OR=1.146; 95% CI: 1.021 to 1.287; p=0.021) were independent predictors of tardive dyskinesia. Discussion: These findings suggest that there is no association between CYP2D6*17and tardive dyskinesia in African psychotic patients on typical antipsychotics. However, more studies with larger sample sizes are required to provide more definitive conclusions regarding the nature of the relationship betweenCYP2D6*17 and tardive dyskinesia. Key words: Tardive dyskinesia, CYP2D*17, typical antipsychotic

Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe

CITATION: Ngara, B., et al. 2021. Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe. BMC Pharmacology and Toxicology, 22:29, doi:10.1186/s40360-021-00497-8.The original publication is available at https://bmcpharmacoltoxicol.biomedcentral.comBackground: Drug potency is a pharmacological parameter defining dose or concentration of drug required to obtain 50% of the drug’s maximal effect. Pharmacokinetic-pharmacodynamic modelling and simulation allows estimation of potency and evaluate strategies improving treatment outcome. The objective of our study is to determine potency of atazanavir in hair, defined as atazanavir level in hair associated with 50% probability of failing to achieve viral load below 1000 copies/ml among adolescents, and explore the effect of participant specific variables on potency. Methods: A secondary analysis was performed on data from a previous study conducted in HIV-infected adolescents failing 2nd line ART from Harare central hospital, Zimbabwe, between 2015 and 2016. We simulated atazanavir concentrations in hair using NONMEM (version 7.3) ADVAN 13, based on a previously established pharmacokinetic model. Logistic regression methods were used for PKPD analysis. Simulations utilising PKPD model focused on estimation of potency and exploring the effect of covariates. Results: The potency of atazanavir in hair was found to be 4.5 ng/mg hair before adjusting for covariate effects. Participants at three months follow-up, reporting adequate adherence, having normal BMI-for-age, and cared for by mature guardians had increased potency of atazanavir in hair of 2.6 ng/mg, however the follow-up event was the only statistically significant factor at 5% level. Conclusion: Atazanavir in hair in the range 2.6 to 4.5 ng/mg is associated with above 50% probability of early viral load suppression. Adherence monitoring to adolescents with lower potency of atazanavir is recommended. The effect self-reported adherence level, BMI-for-age, and caregiver status require further evaluation.https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-021-00497-8Publisher's versio