Pharmacokinetic Interaction Study for Simvastatin and Parsley and Its Plasma Quantification Using LC-MS: A Focus on Drug Metabolic Enzymes

Background: Parsley (Petroselinum crispum L) (PAR) is used widely as an antioxidant, antihyperlipidemic, diuretic, and medication to reduce hypertension. At the same time, conventional drugs such as Simvastatin (SV) are also used to manage hyperlipidemia in hypertensive patients. However, no studies have reported any interactions for the concomitant use of PAR and SV. Objectives: The study aimed to evaluate the enzyme-inducing or inhibiting role of PAR for SV at the level of cytochrome P-450 metabolic enzyme. Methods: This is an open-label (unblinded) study conducted with 24 healthy albino rats (4X6 = 24), atImamAbdulrahman Bin Faisal University, Saudi Arabia, in the year 2018 with protocol approval No. IRB-2018-145-Pharm and approval date 18/04/2018. The animals were administered with a loading single oral dose of SV (80 mg), Clarithromycin (CLAR; 80 mg), Carbamazepine (CBZ; 80 mg), and PAR, i.e., dried herb powder (200 mg), in order to achieve a steady state concentration in the blood. Blood samples were collected at specified time points including pre-dose (0.0) and after-treatment, i.e., 0.5, 1, 1.5, 2, and 3 hours, and centrifuged. The plasma was extracted to analyze for SV by LC-MS using a previously developed method. Results: The analysis of pharmacokinetic parameters revealed enhanced Cmax (mean plasmamaximumconcentration) and AUC0-1 (area under the concentration-time curve) as 2 and 2.2 folds, respectively, for SV+PAR (P < 0.01) as compared to SV alone. A decrease in CL/F (total-body clearance of drug from the plasma) for SV (P < 0.01) and an increased t1/2 (mean half-life) from 3.20 to 6.12 hours for SV co-administered with PAR were observed. Conclusions: Parsley combined with Simvastatin increased the Cmax and AUCs for Simvastatin as 2 and 2.5 folds; thereby, the moderating enzyme-inhibiting role of Parsley for CYP 3A enzyme may be proposed. Hence, caution is required when administering Parsley with Simvastatin for any therapeutic purpose.