A Systematic Review and Meta-Analysis of Doxazosin Pharmacokinetics in Healthy and Diseased Populations

Background: Doxazosin, an α₁-adrenergic antagonist, is commonly used in the management of hypertension and benign prostatic hyperplasia (BPH). Pharmacokinetic (PK) variability across populations may affect drug exposure and clinical response. This systematic review and meta-analysis aimed to summarize PK differences and generate pooled estimates of key parameters, including area under the curve (AUC) and maximum plasma concentration (Cmax). Methods: A systematic search of Google Scholar, PubMed, ScienceDirect, and the Cochrane Library identified 25 eligible studies reporting doxazosin PK data. All extracted AUC and Cmax values were dose-normalized prior to synthesis to ensure comparability across different doses and formulations. A random-effects meta-analysis was performed using the metafor package in R to estimate pooled dose-normalized AUC and Cmax while accounting for between-study variability. Heterogeneity was assessed using the I² statistic. Sensitivity analyses—including leave-one-out diagnostics and Baujat plots—were used to identify influential studies. Publication bias and small-study effects were evaluated through funnel plots, trim-and-fill procedures, and Egger’s regression test. Meta-regression analyses examined the influence of age and body weight on PK parameters. Results: The meta-analysis produced pooled dose-normalized estimates for AUC and Cmax, with high heterogeneity across studies (I² ≈ 90%). Leave-one-out analyses demonstrated stable pooled estimates; for dose-normalized AUC, exclusion of three influential studies reduced heterogeneity to 82% with only a modest decrease in the pooled mean. Baujat plots identified a small number of studies as key contributors to heterogeneity, while most exerted minimal influence. Funnel plots showed notable asymmetry for both AUC and Cmax, and trim-and-fill analyses suggested possible small-study effects; however, adjusted pooled estimates remained consistent. Egger’s regression confirmed significant asymmetry for dose-normalized AUC (t = 4.41, p = 0.0003) and Cmax (t = 4.35, p = 0.0001). Meta-regression revealed that body weight significantly reduced Cmax, whereas age had no significant effect on either AUC or Cmax. Conclusions: This systematic review and meta-analysis provide a comprehensive evaluation of doxazosin PK across diverse populations. Despite normalization, substantial variability remained in AUC and Cmax, related in part to ethnicity, hepatic impairment, dosage formulation, and body weight. While pooled estimates offer valuable summary reference points, the high heterogeneity and evidence of small-study effects highlight the need for more standardized PK trials and patient-level analyses to better support individualized dosing strategies.