Format

Send to

Choose Destination

See 1 citation found by title matching your search:

J Pharmacol Sci. 2019 Feb;139(2):65-71. doi: 10.1016/j.jphs.2018.05.013. Epub 2018 Dec 11.

Reduced variability in tacrolimus pharmacokinetics following intramuscular injection compared to oral administration in cynomolgus monkeys: Investigating optimal dosing regimens.

Author information

1
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
2
College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongbuk, South Korea.
3
School of Pharmacy, University of Nottingham, Nottingham, UK.
4
School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
5
College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, South Korea.
6
School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea. Electronic address: bsshin@skku.edu.
7
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: kmhyj111@gmail.com.

Abstract

Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that Cpeak, Ctrough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies.

KEYWORDS:

Cynomolgus monkey; Intra-individual variability; Intramuscular injection; Tacrolimus

PMID:
30573325
DOI:
10.1016/j.jphs.2018.05.013
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center