Comparative Pharmacokinetics of Nimodipine in Rat Plasma and Tissues Following Intraocular, Intragastric, and Intravenou
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Research Article Comparative Pharmacokinetics of Nimodipine in Rat Plasma and Tissues Following Intraocular, Intragastric, and Intravenous Administration Fang Li,1,2 Qingsong Fei,1 Dan Mao,1 Qiaoyun Si,1 Manman Dai,1 Qun Ma,1 Huimin Zhang,1 Luyu Bai,1 and Ning He1,3,4,5,6
Received 14 May 2020; accepted 22 July 2020 Abstract. We investigated the pharmacokinetics of nimodipine (NMD) in rats plasma and tissues following intraocular (io), intragastric (ig), and intravenous (iv) administration at doses of 5.0 mg/kg io and iv and 10.0 mg/kg ig. After a single dose of NMD, plasma, heart, liver, spleen, lung, kidney, and brain samples were collected at the scheduled time points. The concentration of NMD in rat plasma and tissues was determined by high-performance liquid chromatography, and the main pharmacokinetic parameters were calculated and compared. NMD was rapidly absorbed and reached the maximum plasma concentration in approximately 5 min after io administration. The absolute bioavailability after io administration was higher than that after ig administration (40.05% vs. 5.67%). There were significant differences in the tissue distribution of NMD with different administration routes. After io administration, NMD was distributed more in the lung, spleen, and brain tissues, and less in the kidney. The maximum drug concentration after io administration in the heart, liver, spleen, lung, kidney, and brain was 1.00, 0.47, 2.02, 1.47, 0.22, and 5.79 times higher than that after via ig administration, and the area under the curve value was 0.59, 0.78, 1.71, 1.84, 0.25, and 4.59 times greater, respectively. Nimodipine appears to achieve systemic effects via io administration. Compared with ig, io administration could significantly increase NMD distribution in the brain tissue, indicating that NMD could be delivered to the brain via io administration. KEY WORDS: nimodipine; ocular administration; pharmacokinetics; tissue distribution.
INTRODUCTION The dihydropyridine calcium antagonist nimodipine (NMD) is a Food and Drug Administration-approved drug for the treatment of subarachnoid hemorrhage. Common clinical dosage forms of NMD include plain tablets, capsules, and injections (1). NMD belongs to class II of the Biopharmaceutical Classification System, and its clinical application limited by low
Fang Li and Qingsong Fei contributed equally to this work. 1
Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, No. 1, Qianjiang Road, Hefei, 230012, Anhui, China. 2 College of Biology and Pharmaceutical Engineering, West Anhui University, Lu’an, 237012, China. 3 Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, China. 4 Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China. 5 Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China. 6 To whom correspondence should be addressed. (e–mail: [email protected])
dissolving capacity and first-pass effects on low bioavailability. Bayer’s NM
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