The effect of modulated electro-hyperthermia on the pharmacokinetic properties of nefopam in healthy volunteers: A randomised, single-dose, crossover open-label study

Figures & data

Table 1. Mean demographic data of the subjects who enrolled in the study (n = 12).

	Parameter
	Sex	Age (years)	Height (cm)	Weight (kg)	BMI (kg/m^2)
	Male 4 Female 8
Mean		33.7	162.4	57.8	21.7
Minimum		19	155.4	45.5	18
Maximum		53	177.5	75.4	24.8

Figure 1. Temperature measurements of the abdominal area were repeated immediately after the first modulated electro-hyperthermia and ranged from 39.8–40.9 °C (mean 40.5 °C), indicating an average surface temperature increase of 4 °C.

Table 2. The temperature of the abdominal area of participants who underwent modulated electro-hyperthermia (n = 12).

	Parameter (°C)
	0 min	10 min	20 min	60 min
Mean	36.5	36.9	38.1	40.5
Minimum	36.4	36.6	37.4	39.8
Maximum	36.9	37.4	38.6	40.9

0 min, the abdominal temperature was measured before modulated electro-hyperthermia; 10 min, 20 min, and 60 min, the abdominal temperatures were measured 10 min (100 W), 20 min (120 W), and 60 min (150 W) after modulated electro-hyperthermia, respectively.

Figure 2. (A) The mean plasma concentration-time profiles of nefopam after the uptake of nefopam alone or in combination with modulated electro-hyperthermia. The data are presented as means ± standard error. (B) The mean plasma concentration-time profiles of nefopam after the uptake of nefopam alone or in combination with modulated electro-hyperthermia from 0 h to 6 h.

Table 3. Pharmacokinetic (PK) parameters of nefopam (n = 12).

	Nefopam 30 mg		Nefopam 30 mg + modulated electro-hyperthermia
PK parameter	Mean	SE	Mean	SE	p value
Cmax (ng/mL)	32.18	3.16	42.42	5.32	0.0087
AUClast (h × ng/mL)	253.72	29.49	276.56	36.41	0.3654
AUCinf (h × ng/mL)	308.98	38.65	342.52	48.13	0.3411
Tmax (h)	2.08	0.21	1.58	0.23	0.0470
t1/2 (h)	8.47	0.82	9.40	0.97	0.1656
CL/F (L/h)	140.39	49.65	142.80	53.70	0.3411
Vd/F (L)	1198.71	140.19	1254.50	155.07	0.6194

Values are presented as the arithmetic mean. SE, standard error; C_max, maxinum plasma concentration; AUC_last, area under the plasma concentration-time curve until the final time point; AUC_inf, area under the curve extrapolated to infinity; T_max, time to C_max; t_1/2, terminal half-life; CL/F, apparent total clearance after oral administration; Vd/F, apparent volume of distribution after oral administration.

Table 4. Statistical analysis of nefopam (n = 12).

	Geometric LS mean		Geometric LS mean ratio
Pharmacokinetic parameter	Nefopam30 mg	Nefopam 30 mg + modulated electro-hyperthermia	Point estimate	90% confidence interval
Cmax (ng/mL)	29.65	37.97	1.2804	1.1155–1.4696
AUClast (h × ng/mL)	217.92	229.09	1.0512	0.9555–1.1566
AUCinf (h × ng/mL)	262.44	278.51	1.0612	0.9528–1.1819

These values are presented as the geometric means (CV%). The 90%CIs for parameters were within the bioequivalence limit of 0.8 to 1.25. The point estimate is geometric mean ratio. C_max, maximum plasma concentration; AUC_last, area under the curve until the final time point; AUC_inf, area under the curve extrapolated to infinity

least-squares mean (LS).