Geographic differences in the target-controlled infusion estimated concentration of propofol: bispectral index response curves.

PURPOSE: Variability in drug responses could result from both genetic and environmental factors. Thus, drug effect could depend on geographic location, although regional variation is not generally acknowledged as a basis for stratification. There is evidence that the pharmacokinetic set developed in a European population for the target-controlled infusion (TCI) of propofol does not apply in Chinese patients; however, we are not aware of previous studies comparing the estimated concentration-bispectral index (BIS) response of Caucasian patients in Europe with that of Chinese patients in China. METHODS: The Diprifusor™ TCI pump, incorporating the pharmacokinetic model proposed by Marsh et al., was applied to 30 Caucasian patients in Austria and 30 Chinese patients in China. The estimated plasma concentration (C(p)) of propofol for the two groups was set at 1 µg·mL(-1) and increased by 1 µg·mL(-1) every minute to gradually reach 5 µg·mL(-1) after 5 min. The BIS values were fitted against the estimated C(p) and the predicted effect-site concentration (C(e)) in a sigmoid E(max) model. RESULTS: The sigmoid E(max) curves were shifted significantly to the left in the Chinese group compared with the Austrian group. After 5 min, the BIS value in the Chinese group was lower than in the Austrian group (mean ± standard deviation [SD], 47.2 ± 3.6 vs 63.6 ± 5.4, respectively; P = 0.0006). The estimated C(p) at loss of consciousness (LOC), predicted C(e) at LOC, and time to LOC, were lower in the Chinese group than in the Austrian group (3.3 ± 0.8 µg·mL(-1), 1.6 ± 0.4 µg·mL(-1), 2.8 ± 0.6 min, respectively, vs 4.6 ± 2.8 µg·mL(-1), 2.4 ± 1.5 µg·mL(-1), 3.9 ± 0.5 min, respectively; P < 0.0001). CONCLUSION: When propofol is given using the same TCI protocol, Chinese patients in China lost consciousness faster and at a lower estimated plasma concentration than Caucasians in Austria. Larger studies are needed to map geographically appropriate TCI infusion models.

Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage.

BACKGROUND: Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. METHODS: Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. RESULTS: Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/- 59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148 +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8 min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively). CONCLUSIONS: The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.