Pharmacokinetics and bioavailability of tuftsin-derived T peptide, a promising antitumor agent, in beagles

Gu, Ruixia; He, Yuanqing; Han, Shuang; Yuan, Si-Ming; An, Yinghong; Zhang, Meng; Zhu, Xue-Ming; Gan, Hui; Wu, Zhuona; Li, Jian; Zheng, Ying; Zhang, Ling; Gao, Lei; Dou, Guifang

doi:10.1016/j.dmpk.2015.08.005

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…On the other hand, obvious accumulation of ibuprofenamine and Ibuprofen were found probably related to ibuprofenamine hydrochloride have high tissue affinity and the tissue half time would be much longer than in blood, thus causing an accumulation tendency in multiple dosing when ibuprofenamine was released from the tissue and entered into the blood again. 15–18 The results of the multiple dosing pharmacokinetics indicated that the dosing interval of ibuprofenamine hydrochloride should be extended in the following clinical phase study.…”

Section: Discussionmentioning

confidence: 99%

Safety, Tolerability, and Pharmacokinetics of Ibuprofenamine Hydrochloride Spray (NSAIDs), a New Drug for Rheumatoid Arthritis and Osteoarthritis, in Healthy Chinese Subjects

Xie¹,

Xue²,

Wei³

et al. 2021

DDDT

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Background Ibuprofenamine hydrochloride spray is novel transdermal nonsteroidal anti-inflammatory drugs (NSAIDs), under clinical development for the treatment of Rheumatoid Arthritis and Osteoarthritis as a novel transdermal drug. Methods A single and multiple ascending dose study investigated the safety, tolerability and pharmacokinetics of ibuprofenamine hydrochloride in healthy Chinese subjects. A total of 34 subjects (single-dose study: 34 subjects and multiple-dose study: 20 subjects) were involved in the trial. In the single-dose study, subjects were assigned to one of the four groups received 35, 70, 140, 280 mg. In the 70 mg and 140 mg treatment groups, subjects received one dose on the first day and twice a day from day 6 to 12. The starting dose was determined considering the no observed adverse effect level based on preclinical studies, and the dose escalations in subsequent cohorts were decided based on safety, tolerability, and pharmacokinetic data from previous dose cohorts. Results After a single dose, both ibuprofenamine and ibuprofen plasma exposure showed a more than dose-proportional increase across a dose range of 35–280 mg. After multiple dosing, both ibuprofenamine and ibuprofen steady-state exposure increased obviously more than dose-proportional manner across the evaluated dose range (twice a day for 7 days) resulted in obvious accumulation. Single or multiple doses of ibuprofenamine hydrochloride were generally well tolerated and no obvious skin irritation was observed. Conclusion Ibuprofenamine hydrochloride exhibited a safety and pharmacokinetic profile that supports its future investigation as a potential therapeutic for Rheumatoid Arthritis and Osteoarthritis.

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Section: Discussionmentioning

confidence: 99%

Safety, Tolerability, and Pharmacokinetics of Ibuprofenamine Hydrochloride Spray (NSAIDs), a New Drug for Rheumatoid Arthritis and Osteoarthritis, in Healthy Chinese Subjects

Xie¹,

Xue²,

Wei³

et al. 2021

DDDT

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Pharmacokinetics, safety and tolerability of the novel β‐hCG derived immunomodulatory compound, EA‐230

Groenendael

Aarnoutse

Kox

et al. 2019

Brit J Clinical Pharma

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Aims EA‐230 is a newly developed synthetic linear tetrapeptide (AQGV) derived from the chorionic gonadotropin hormone (β‐hCG). We investigated the pharmacokinetics, safety and tolerability of EA‐230 in healthy subjects using different administration strategies. Methods Double‐blind, randomized, placebo‐controlled, dose‐escalating phase I studies in healthy subjects using intravenous administration were conducted. In the single dosage study, 32 subjects were assigned to four single dosage groups (1, 3, 10 or 30 mg/kg). In the multiple dosage study, 24 subjects were assigned to three dosage groups (10, 20 or 30 mg/kg, thrice daily for 3 days). In the continuous dosage study, 24 subjects were assigned to three dosage groups (15, 30, or 90 mg/kg/hour for 2 hours). Pharmacokinetics, safety and tolerability assessments were performed up to 14 days. Results The highest dosage of EA‐230 (continuous infusion of 90 mg/kg/hour for 2 hours) showed more than proportional increases in exposure (Cmax136%; AUC0‐last137%), a large volume of distribution (geometric mean and 95% CI: 13 [3–58] L/kg), a high clearance rate (26 [15–43] L/h/kg), and a short half‐life (0.35 [0.13–1.0] minutes). EA‐230 was well tolerated and no safety concerns were observed. Conclusion These dose‐escalating phase I studies with different administration strategies reveal a pharmacokinetic profile of EA‐230 with a large volume of distribution and a short half‐life. Furthermore, EA‐230 was well tolerated and no safety issues emerged. These results have enabled further clinical development in a phase IIa trial assessing the pharmacodynamics of this compound during systemic inflammation described elsewhere in this issue.

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Pharmacokinetics and bioavailability of tuftsin-derived T peptide, a promising antitumor agent, in beagles

Cited by 2 publications

References 26 publications

Safety, Tolerability, and Pharmacokinetics of Ibuprofenamine Hydrochloride Spray (NSAIDs), a New Drug for Rheumatoid Arthritis and Osteoarthritis, in Healthy Chinese Subjects

Safety, Tolerability, and Pharmacokinetics of Ibuprofenamine Hydrochloride Spray (NSAIDs), a New Drug for Rheumatoid Arthritis and Osteoarthritis, in Healthy Chinese Subjects

Pharmacokinetics, safety and tolerability of the novel β‐hCG derived immunomodulatory compound, EA‐230

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