Pharmacokinetic Analysis, Analgesic Effects, and Adverse Effects of Tapentadol in Cancer Patients with Pain

• Published in: Biological & pharmaceutical bulletin Vol. 43; no. 6; pp. 1000 - 1006
• Main Authors: Homma, Masashi, Kokubun, Hideya, Okuwaki, Kosuke, Katada, Chikatoshi, Hayashi, Norihito, Kanai, Akifumi, Koizumi, Wasaburo, Atsuda, Koichiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.06.2020; Japan Science and Technology Agency
• Subjects: Adult; Aged; Aged, 80 and over; Analgesics; Analgesics, Opioid - adverse effects; Analgesics, Opioid - blood; Analgesics, Opioid - pharmacokinetics; Analgesics, Opioid - therapeutic use; Bilirubin; Cancer; cancer pain; Cancer Pain - blood; Cancer Pain - drug therapy; Cancer Pain - metabolism; covariate; Female; Humans; liver function; Male; Middle Aged; Opioids; Pain; pharmacokinetic analysis; Pharmacokinetics; Side effects; Statistical analysis; tapentadol; Tapentadol - adverse effects; Tapentadol - blood; Tapentadol - pharmacokinetics; Tapentadol - therapeutic use; Treatment Outcome; cancer pain; pharmacokinetic analysis; covariate; tapentadol; liver function
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.b20-00084

In this study, we conducted a pharmacokinetic analysis of tapentadol (TP) in Japanese patients with cancer pain and identified covariates influencing pharmacokinetic parameters. In addition, the analgesic effects and adverse effects of TP were investigated. Data were collected from in-patients with cancer pain who had been administered TP as an extended-release formula. The median (range) estimated clearance (CL/F) and distribution volume (Vd/F) of TP were 86.7 (31.3–213.7) L/h and 1288 (189–6736) L, respectively. There was a strong negative correlation between CL/F and age, Child–Pugh score, and albumin-bilirubin (ALBI) score. The subjects were further divided into two groups according to the factors highly correlated with CL/F. The CL/F of patients in the Child–Pugh B group was 0.46-times that of patients in the Child–Pugh A group. In addition, the CL/F of patients with an ALBI score > −2.40 was 0.56-times that of patients with ALBI scores ≤−2.40, and both differences were statistically significant (p < 0.05). The mean intensity of pain over 24 h was investigated daily from before starting TP for the first 7 d of the treatment. TP reduced pain in six of nine patients; the mean pain visual analogue scale score decreased significantly from 59.2 mm before administration to 42.5 mm at days 5–7. Overall, the Child–Pugh and ALBI scores significantly affected the clearance of TP, which was reduced in patients with impaired liver function. These results suggest that TP is an opioid with a sufficient analgesic effect for cancer patients.