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Abstract
To determine blood alcohol concentration (BAC) by extrapolation, an understanding of basal pharmacokinetics is indispensable. Breath alcohol concentration (BrAC) has been used for the determination of body alcohol concentration replaced by BAC in Korea. Therefore, the determination of BAC/BrAC ratio is a key problem in alcohol pharmacokinetics. Among several factors, the ingested dose of alcohol and the allelic variation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) are the most significant factors influencing the pharmacokinetic parameters, particularly in the absorption and elimination phases. This study shows a detailed pharmacokinetic analysis of BAC and BrAC associated with genetic polymorphism including ALDH2 in 42 healthy Korean men. The change in the alcohol dose ingested influenced the maximum concentration (Cmax), the time to reach Cmax (Tmax), the absorption rate constant (K01), the area under the concentration-time curve (AUClast), and the hourly elimination rate. The conversion of wild-type 487Glu (ALDH2∗1) to 487Lys (ALDH2∗2) in human ALDH2 resulted in changes in Cmax (ALDH2∗1/∗1, 0.03±0.01 g/dL [±standard deviation] vs. ALDH2∗1/∗2, 0.05±0.004 g/dL [P<0.01]), AUClast (ALDH2∗1/∗1, 4.48±2.19 g∙ min/dL vs. ALDH2∗1/∗2, 7.52±1.26 g∙min/dL [P<0.05]), and the BAC elimination rate (ALDH2∗1/∗1, 0.05±0.02 g/L/hr vs. ALDH2∗1/∗2, 0.09±0.01 g/L/hr [P<0.05]). Moreover, the comparison of BAC and BrAC by Bland-Altman plot showed good agreement, suggesting that the measurement of BrAC can be a good alternative for the determination of BAC, particularly in the post-absorption phase. These results provide fundamental information about the pharmacokinetics of alcohol and the determination of BAC in forensics.
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Fig. 1.
Mean breath alcohol concentration (BrAC) and blood alcohol concentration (BAC) versus time profiles in group A (0.5 g/kg) and group B (0.8 g/kg) participants. After drinking alcohol within a period of 20 minutes, BrAC and BAC were determined every 30 or 60 minutes (30, 60, 90, 120, 150, 180, 240, 300, 360, and 420 minutes) as described in the Materials and Methods section.
Fig. 2.
Bland-Altman plot of each participant's difference (blood alcohol concentration [BAC]-breath alcohol concentration [BrAC]) against the mean of the two measurements ([BAC+BrAC]/2). Empty circles and filled circles represent data from group A (0.5 g/kg) and group B (0.8 g/kg), respectively. The horizontal lines show a mean bias of -0.00075, and 95% lower and upper limits of agreement of -0.1136 and 0.1121.
Table 1.
Pharmacokinetic parameters in group A (0.5 g/kg, n=20) and group B (0.8 g/kg, n=22) participants
Table 2.
Individual elimination rate (g/L/hr) of breath alcohol concentration and blood alcohol concentration calculated by linear regression
Table 3.
Allelic and genotypic frequencies of ADH1B, ADH1C, and ALDH2 polymorphisms
Table 4.
Comparison of pharmacokinetic parameters according to the ADH1B, ADH1C, and ALDH2 genotypes in group A participants
| Parameter | ADH1B (His47Arg, rs1229984, A to G) | ADH1C (Ile349Val, rs698, A to G) | ALDH2 (Glu487Lys, rs671, G to A) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| AA (n=14) | AG (n=6) | P-valuea) | AA (n=17) | AG (n=3) | P-valuea) | GG (n=16) | AG (n=4) | P-valuea) | |
| Breath | |||||||||
| Tmax (min) | 51.42±21.79 | 50.00±24.49 | 0.8575 | 49.41±21.06 | 60.00±30.00 | 0.4893 | 52.50±23.24 | 45.00±17.32 | 0.6070 |
| Cmax (g/dL) | 0.04±0.01 | 0.04±0.01 | 0.7724 | 0.04±0.01 | 0.04±0.01 | 0.6714 | 0.03±0.01 | 0.05±0.003 | 0.0060b) |
| max AUClast (g∙min/dL) | 4.91±2.36 | 5.26±2.17 | 0.5634 | 4.93±2.37 | 5.52±1.61 | 0.5964 | 4.35±1.92 | 7.67±1.41 | 0.0061b) |
| K01 (1/min) | 0.26±0.07 | 0.24±0.02 | 0.6801 | 0.26±0.07 | 0.24±0.02 | 0.9578 | 0.26±0.07 | 0.23±0.01 | 0.0182c) |
| 01 KM (g/dL) | 3.74±0.31 | 3.79±0.05 | 0.6801 | 3.75±0.28 | 3.78±0.02 | 0.711 | 3.75±0.29 | 3.80±0.04 | 0.5708 |
| VM (1/min) | 1.15±0.13 | 1.17±0.06 | 0.4579 | 1.15±0.12 | 1.16±0.09 | 0.9578 | 1.17±0.12 | 1.10±0.03 | 0.2568 |
| Elimination rate (g/L/hr) | 0.06±0.03 | 0.07±0.02 | 0.4831 | 0.06±0.03 | 0.07±0.02 | 0.4585 | 0.06±0.02 | 0.09±0.01 | 0.0061b) |
| Blood | |||||||||
| Tmax (min) | 38.57±14.06 | 35.00±12.25 | 0.5829 | 37.06±13.12 | 40.00±17.32 | 0.7245 | 39.38±14.36 | 30.00±0 | 0.2083 |
| Cmax (g/dL) | 0.03±0.01 | 0.04±0.01 | 0.5087 | 0.03±0.01 | 0.03±0.01 | 0.791 | 0.03±0.01 | 0.05±0.004 | 0.0093b) |
| AUClast (g∙min/dL) | 4.98±2.27 | 5.35±2.78 | 0.7415 | 5.16±2.48 | 4.69±1.95 | 0.7913 | 4.48±2.19 | 7.52±1.26 | 0.0182c) |
| K01 (1/min) | 0.24±0.13 | 0.23±0.03 | 0.4095 | 0.24±0.12 | 0.25±0.02 | 0.9578 | 0.26±0.11 | 0.18±0.12 | 0.1859 |
| KM (g/dL) | 3.67±0.60 | 3.80±0.07 | 0.8046 | 3.69±0.54 | 3.82±0.10 | 0.711 | 3.68±0.56 | 3.84±0.05 | 0.3447 |
| VM (1/min) | 1.31±0.36 | 1.23±0.17 | 0.8046 | 1.31±0.33 | 1.15±0.11 | 0.3683 | 1.24±0.18 | 1.45±0.63 | 0.7768 |
| Elimination rate (g/L/hr) | 0.06±0.03 | 0.06±0.02 | 0.7415 | 0.06±0.03 | 0.06±0.02 | 0.6338 | 0.05±0.02 | 0.09±0.01 | 0.0182c) |
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