We used mathematical modeling in order to determine the pharmacodynamic relationship between antihypertensive drugs atenolol and valsartan, by evaluating their effects on heart rate (HR), systolic blood pressure (SP) and diastolic blood pressure (DP). A group of twelve healthy male volunteers received a single oral dose of 100 mg of atenolol and 160 mg of valsartan, both separately and in combination. Pharmacokinetic (PK), pharmacokinetic/pharmacodynamic (PK/PD) and pharmacodynamic (PD) systems were proposed and PD model of atenolol and valsartan concentration-time profiles and PK/PD model of blood pressure and heart rate effects after administration of single doses of atenolol and valsartan and their combination were constructed. Parameters of PD system, such as gain and mean effect time, were obtained by analysis of PK and PK/PD systems. Modeling of PK and PK/PD systems and their analysis to obtain the PD results could considerably change the view o treatment of individual diseases in terms of greater knowledge of pharmacokinetics and pharmacodynamics of drugs.
The removal efficiency of pharmaceutical compounds in wastewater treatment can be significantly influenced by seasonal variations and the presence of vegetation. This study evaluates the removal efficiencies of five pharmaceutical compounds – Cefadroxil (CFL), Ciprofloxacin (CIP), Cefpodoxime (CFD), Atenolol (ATN) and Avil-25 (AVL) – in non-planted (CW2) and planted (CW1) constructed wetlands across various parameters including Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Total Suspended Solids (TSS), Alkalinity, Nitrate, and Phosphate during winter and summer seasons. Results indicate that CW1 consistently outperforms CW2 in all parameters and seasons. For example, CW1 achieved 54.28% BOD removal for CFL in winter compared to CW2's 39.67%, with summer values reaching 79.6% and 69.7%, respectively. The superior performance of CW1 was also observed for COD and other parameters, with phosphate removal reaching 94% in summer. The results of HPLC analysis indicated that CW1 showed better removal efficiencies of Cefadroxil (56.94%), Ciprofloxacin (90%), and Avil-25 (99.7%) than CW2. Even though Cefpodoxime showed low removal efficiency in both systems, CW1 still performed slightly better (13.99% vs. 0.7%). Atenolol removal was particularly notable in CW1 (93.79%), significantly outperforming CW2. Hazard quotient assessments revealed lower risks associated with pharmaceutical residues in CW1. For example, Ciprofloxacin's hazard quotient was reduced from 16% in CW2 to 10% in CW1, underscoring the effectiveness of vegetation in mitigating environmental risks. Atenolol showed a significant hazard quotient reduction from 2% in CW2 to less than 0.5% in CW1, while Avil-25's hazard quotient was negligible in CW1 compared to 4% in CW2. It was also concluded that vegetation positively influenced the treatment efficacy of constructed wetlands for pharmaceuticals with reduced eco-toxicity and the associated risks.
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