End-stage renal disease (ESRD) patients are mostly managed with maintenance hemodialysis (MHD). ESRD patients on MHD also present with many complications, such as anemia, hyperparathyroidism, and hepatitis prevalence. This study depicts the real-world scenario of anemia among MHD and end-stage renal disease patients in the Pakistani population. A retrospective, multicentric, and real-world data analytical study was conducted at 4 dialysis centers in Pakistan. The study had a sample size of n = 342 patients on maintenance hemodialysis. The data were gathered from the medical records of patients. Data analysis was performed using STATA Version 16. Statistical significance was gauged at a 0.05 level of significance. According to our results, the mean age of the patients was 45 (±15) years. Most of the patients were male (n = 234, 68.4%), whereas 58.1% of the patients were maintained on twice-weekly hemodialysis. The most commonly reported comorbidities were hypertension and diabetes mellitus. The frequency of dialysis ( P < 0.01) and comorbidities ( P = 0.009) had a significant association with anemia in MHD patients. The majority of the patients had hyperparathyroidism (52%) with anemia. Upon performing binary logistic regression, multivariate analysis displayed a similar odds value for having anemia in patients with every additional month in the duration of hemodialysis (OR 1.01, P = 0.001), the odds of anemic patients having a positive antihepatitis-C antibody (OR 2.22, P = 0.013), and the odds of having anemia in patients in the age category below 45 years (OR 1.93, P = 0.013). In conclusion, the study results depict that every additional month in the duration of hemodialysis, age (<45 years), and positive anti-HCV antibody status, these variables were more likely to have anemia in our study MHD patients. While in our final multivariate model, no statistically significant association was observed between hyperparathyroidism and anemia.
Background: Voriconazole an antifungal drug, has a potential for drug-drug interactions (DDIs) with administered drugs. Clarithromycin is a Cytochromes P450 CYP (3A4 and 2C19) enzyme inhibitor, and voriconazole is a substrate and inhibitor of these two enzymes. Being a substrate of the same enzyme for metabolism and transport, the chemical nature and pKa of both interacting drugs make these drugs better candidates for potential pharmacokinetic drug-drug interactions (PK-DDIs). This study aimed to evaluate the effect of clarithromycin on the pharmacokinetic profile of voriconazole in healthy volunteers.Methods: A single oral dose, open-label, randomized, crossover study was designed for assessing PK-DDI in healthy volunteers, consisting of 2 weeks washout period. Voriconazole, either alone (2 mg × 200 mg, tablet, P/O) or along with clarithromycin (voriconazole 2 mg × 200 mg, tablet + clarithromycin 500 mg, tablet, P/O), was administered to enrolled volunteers in two sequences. The blood samples (approximately 3 cc) were collected from volunteers for up to 24 h. Plasma concentrations of voriconazole were analyzed by an isocratic, reversed-phase high-performance-liquid chromatography ultraviolet-visible detector (RP HPLC UV-Vis) and a non-compartmental method.Results: In the present study, when voriconazole was administered with clarithromycin versus administered alone, a significant increase in peak plasma concentration (Cmax) of voriconazole by 52% (geometric mean ratio GMR: 1.52; 90% CI 1.04, 1.55; p = 0.000) was observed. Similarly, the area under the curve from time zero to infinity (AUC0-∞) and the area under the concentration-time curve from time zero to time-t (AUC0-t) of voriconazole also significantly increased by 21% (GMR: 1.14; 90% CI 9.09, 10.02; p = 0.013), and 16% (GMR: 1.15; 90% CI 8.08, 10.02; p = 0.007), respectively. In addition, the results also showed a reduction in the apparent volume of distribution (Vd) by 23% (GMR: 0.76; 90% CI 5.00, 6.20; p = 0.051), and apparent clearance (CL) by 13% (GMR: 0.87; 90% CI 41.95, 45.73; p = 0.019) of voriconazole.Conclusion: The alterations in PK parameters of voriconazole after concomitant administration of clarithromycin are of clinical significance. Therefore, adjustments in dosage regimens are warranted. In addition, extreme caution and therapeutic drug monitoring are necessary while co-prescribing both drugs.Clinical Trial Registration:clinicalTrials.gov, Identifier NCT05380245.
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