ABSTRACT
Background: Rifamycins are a novel class of antibiotics clinically approved for tuberculosis chemotherapy. They are characterized by high inter-individual variation in pharmacokinetics. This systematic review aims to present the contribution of genetic variations in drug-metabolizing enzymes and transporter proteins to the inter-individual variation of rifamycin pharmacokinetics. Method: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The search for relevant studies was done through PubMed, Embase, Web of Science, and Scopus databases. Studies reporting single nucleotide polymorphism in drug transporters and metabolizing enzymes' influence on rifamycin pharmacokinetics were solely included. Two reviewers independently performed data extraction. Results: The search identified 117 articles of which 15 fulfilled the eligibility criteria and were included in the final data synthesis. The single nucleotides polymorphism in the drug transporters SLCO1B1 rs4149032, rs2306283, rs11045819, and ABCB1 rs1045642 for rifampicin, drug metabolizing enzyme AADAC rs1803155 for rifapentine and CES2 c.-22263A>G (g.738A>G) for rifampicin partly contributes to the variability of pharmacokinetic parameters in tuberculosis patients. Conclusion: The pharmacokinetics of rifamycins is influenced by genetic variation of drug-metabolizing enzymes and transporters. Controlled clinical studies are, however, required to establish these relationships.
ABSTRACT
BACKGROUND: Epilepsy is among the most common neurological disorders which is highly treatable with currently available antiepileptic drugs at a reasonable price. In Ethiopia, despite a number of studies revealed high prevalence of epilepsy, little is known on predictors of poorly controlled seizures. Thus, the aim of this study was to assess epilepsy treatment outcome and its predictors among patients with epilepsy on follow-up at the ambulatory care unit of Mizan-Tepi University Teaching Hospital, Southwest Ethiopia. METHODS: A hospital-based cross-sectional study involving patient interview and chart review was conducted from March 10 to April 10, 2018. Drug use patterns and sociodemographic data of the study participants were accustomed to descriptive statistics. Backward logistic regression analysis was done to identify predictors of poor seizure control. Statistical significance was considered at p value <0.05. RESULTS: From a total of 143 studied patients with epilepsy, 60.8% had uncontrolled seizures. Monotherapy (79%) was commonly used for the treatment of seizures, of which phenobarbital was the most commonly utilized single anticonvulsant drug (62.9%). The majority (72.7%) of the patients had developed one or more antiepileptic-related adverse effects. Medium medication adherence (adjusted odds ratio (AOR) = 5.4; 95% CI = 1.52-19.23; p=0.009), poor medication adherence (AOR = 8.16; 95% CI = 3.04-21.90; p=0.001), head injury before seizure occurrence (AOR = 4.9; 95% CI = 1.25-19.27; p=0.02), and seizure attacks ≥4 episodes/week before AEDs initiation (AOR = 8.52; % CI = 2.41-13.45; p=0.001) were the predictors of uncontrolled seizure. CONCLUSIONS: Based on our findings, more than half of the patients with epilepsy had poorly controlled seizures. Nonadherence to antiepileptic drugs, high frequency of seizure attack before AEDs initiation, and history of a head injury before the occurrence of seizure were predictors of uncontrolled seizure. Patient medication adherence should be increased by the free access of antiepileptic drugs and attention should be given for the patients with a history of head injury and high frequency of seizure attacks before AEDs initiation.
