Coadministration of Lidocaine and Recombinant Human Erythropoietin-Beta: Effect on Pain and of Erythropoietin Pharmacokinetics

Shigeki Yamada, Isao Muraoka, Kana Kato, Rie Hiramatsu, Hiroko Ida, Hirohisa Kawahara, Toshitaka Nabeshima

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Abstract

Background: Subcutaneous injections of recombinant human erythropoietin is associated with significant pain at the injection site. The present study evaluated whether lidocaine reduces the pain associated with subcutaneous injection of recombinant human erythropoietin-beta (rhEPO-β) and whether coadministration of lidocaine alters the pharmacokinetics of erythropoietin. Methods: Fifteen hundred units of rhEPO-β (Epogen) or a combination of 1500 units of rhEPO-β and 0.1 mL of 1% lidocaine (Xylocaine) were administered subcutaneously to 4 study subjects. After injections, pain reduction was assessed using visual analog scale (VAS). Blood samples were collected at designated intervals to measure serum erythropoietin (EPO) concentrations. The pharmacokinetic parameters such as area under the serum concentration-time curve (AUC0-48), peak concentration (C max), time to the Cmax (tmax), and terminal elimination half-life (t1/2) were calculated by the usual methods. Results: The values of VAS were 8.3 ± 2.3 and 1.7 ± 1.2 for rhEPO-β alone and the combination with lidocaine, respectively, indicating that injection pain caused by rhEPO-β was reduced by the coadministration of lidocaine. The value of AUC0-48 was 471.2 ± 176.7 (mean ± SD) mIU.mL/h for rhEPO-β and 675.1±292.0 mIU.mL/h for the combination; the value of Cmax was 15.3 ± 3.7 mIU/mL for rhEPO-β and 24.2 ± 8.8 mIU/mL for the combination. The value of tmax was 27.75 ± 23.41 h and 10.50 ± 3.87 h for the combination, and the t1/2 value was 17.91 ± 0.30 h for rhEPO-β and 37.10±10.32 h for the combination. However, no significant differences in the pharmacokinetic parameters of EPO were observed between rhEPO-β injection with or without lidocaine. Conclusion: No significant differences in the bioavailability parameters were observed between rhEPO-β alone and the combination of rhEPO-β and lidocaine. Coadministration of lidocaine seems to be effective for pain caused by subcutaneous injection of rhEPO-β without causing any problems in clinical safety.

Original languageEnglish
Pages (from-to)429-433
Number of pages5
JournalJournal of Applied Research
Volume3
Issue number4
Publication statusPublished - 01-09-2003
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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