The effect of modulated electro-hyperthermia on the pharmacokinetic properties of nefopam in healthy volunteers: A randomised, single-dose, crossover open-label study.
OBJECTIVE
Nefopam is a widely available analgesic for the management of pain. The aim of this study was to reveal the effect of regional hyperthermia of the abdominal area on the pharmacokinetics of nefopam.


METHODS
A randomised, single-dose, crossover, open-label study was conducted to reveal the effect of hyperthermia using modulated electro-hyperthermia on the pharmacokinetics of nefopam. The pharmacokinetics of orally administered nefopam without hyperthermia was studied in 12 healthy volunteers and then 7 days later they were treated with nefopam plus modulated electro-hyperthermia to the abdominal area for 1 h. Blood samples were collected up to 24 h after the drug administration. From the blood concentration-time curve, the maxinum plasma concentration (C(max)), time to C(max) (T(max)) and the area under the curve (AUC) were obtained. The safety and tolerability of these treatments were also assessed.


RESULTS
The geometric mean ratios (GMRs) ((nefopam + modulated electro-hyperthermia)/nefopam) and the associated 90% confidence intervals (CIs) for C(max), AUC(last) and AUC(inf) were 1.2804 (1.1155∼1.4696), 1.0512 (0.9555∼1.1566) and 1.0612 (0.9528∼1.1819), respectively. The increase in C(max) was statistically significant, and T(max) was significantly shortened.


CONCLUSIONS
The significant increase in C(max) and decrease in T(max) indicated that modulated electro-hyperthermia increased the absorption of the orally administered nefopam, thereby transitionally increasing the blood concentration of the drug. The AUC is an important parameter that contributes to the therapeutic effect of drugs. The lack of significant change in AUC suggests that modulated electro-hyperthermia may increases the absorption of orally administered drugs without increasing the systemic adverse effect of the drugs.
a Department of Radiation Oncology , Chonbuk National University Hospital , Jeonju , Jeonbuk , Republic of Korea .|c Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital , Jeonju , Jeonbuk , Republic of Korea.
Sun Young
SY
Lee
b Clinical Pharmacology Unit and Biomedical Research Institute, Chonbuk National University Hospital , Jeonju , Jeonbuk , Republic of Korea , and.|c Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital , Jeonju , Jeonbuk , Republic of Korea.
Min-Gul
MG
Kim
D000005:Abdomen; D000284:Administration, Oral; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004566:Electrodes; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000379:methods*; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009340:Nefopam / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D018712:Analgesics, Non-Narcotic; D009340:Nefopam
Clinical trial modulated electro-hyperthermia; nefopam; pharmacokinetics