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Similarity of Insulin Detemir Pharmacokinetics, Safety, and Tolerability Profiles in Healthy Caucasian and Japanese American Subjects
Author(s) -
Jhee Stan S.,
Lyness William H.,
Rojas Patrick B.,
Leibowitz Mark T.,
Zarotsky Victoria,
Jacobsen Lisbeth V.
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270003262949
Subject(s) - insulin detemir , medicine , pharmacokinetics , tolerability , adverse effect , insulin , hypoglycemia , dosing , anesthesia , endocrinology , insulin glargine
The objective of this study was to compare the pharmacokinetics of insulin detemir in three ascending doses in healthy Japanese and Caucasian subjects. This was an open‐label, single‐center, parallel‐group design evaluating 30 subjects (15 Japanese and 15 Caucasians). Subjects received a total of three subcutaneous injections (one injection per visit) of insulin detemir (0.19, 0.38, 0.75 U/kg [1 U = 24 nmol]) in ascending order. Following drug administration, subjects received intravenous glucose in 0.5‐mg/kg/min increments every 30 minutes, followed by a constant rate of 2.0 mg/kg/min for up to 12 hours. For pharmacokinetic evaluations, serial blood sampling was performed over a period of 30 hours after dosing. Of the subjects, 36 were enrolled, and 30 completed the study. There was a linear dose‐response relationship between the three ascending insulin detemir doses and serum insulin detemir AUC values for both the Japanese and Caucasian subjects. The two dose‐response regression lines had equivalent slopes but slightly different intercepts (although not statistically significant). This difference may be due to variation in AUC, body weight differences, or chance. Six subjects discontinued the study, 2 as a result of adverse events (blood draw–related ecchymosis and hypoglycemia). The most frequent treatment‐emergent adverse events (TEAE) were headache, dizziness, and reactions related to blood draws/infusion sites. All TEAEs were mild to moderate in severity. The results show that an increase in insulin detemir dose will result in a similar increase in insulin detemir concentration in the two ethnic groups. Therefore, therapeutic dosing of insulin detemir is expected to be similar in both ethnic groups, with no special dose adjustment or algorithm based on race. Insulin detemir at 0.19, 0.38, and 0.75 U/kg was generally well tolerated in both Japanese and Caucasian subjects.