Document Type : Research articles

Authors

• Rizwan Ahmad ¹
• Niyaz Ahmad ²
• Dhafer Mahdi Alshayban ³
• Muntathir Ali Alamer ⁴
• Ali Hassan Mohammed Alkhalifah ⁴
• Hamzah Mohammed Almomatten ⁴

¹ Natural Products and Alternative Medicines, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

² Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

³ Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

⁴ College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

Abstract

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), at Imam Abdulrahman 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 plasma maximum concentration) and AUC0-∞
(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 moder-
ating 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.

Keywords

• Cytochrome P450
• CYP3A4
• Hyperlipidemia
• Parsley
• Pharmacokinetics
• Simvastatin