Optimized bio-analytical methods development and comparative pharmacokinetic studies of four antidepressants in Egyptian population based on gender difference

Abstract

The pharmacokinetics (PK) and pharmacodynamics of many oral antidepressants (OADs) vary substantially among different genders and ethnicities. Likewise is their therapeutic effectiveness, time to response and the incidence of adverse drug events. The aim of this study is to compare the PK of four OADs (desvenlafaxine; DSV, venlafaxine; VLX, escitalopram; ESP, and agomelatine; AGT) among Egyptian males and females.In this study, LC-MS/MS methods were developed and validated for determining the four OADs in human plasma. Samples were prepared by liquid-liquid extraction. Chromatographic separation was performed on reversed-phase C18 columns followed by positive-ion electrospray ionization and MS/MS detection. The assays were applied for the assessment of PK parameters in human volunteers (n = 95).The developed methods were linear, accurate, and precise for the determination of DSV, VLX, ESP and AGT with extraction recovery of 90 ± 2.0, 98 ± 1.0, 90 ± 1.3 and 87 ± 4.3%, respectively. OADs levels were successfully measured in subjects' plasma and PK parameters were calculated.A prevalent inter-individual variation in PK of the studied OAD was observed. The PK profile of DSV, VLX or ESP did not vary significantly between male and female subjects (p = 0.07–0.98; confidence level (CL) = 95) while the PK of AGT exhibited a significant gender-based variation in both the Cmax and the AUC∞ (p = 0.047 and 0.0015; CL = 95).Our results highlight the significance of therapeutic drug monitoring of OADs. Further, it indicates the dose adjustment based on gender difference may not be relevant for DSV, VLX and ESP while it may be considered for AGT.