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The values of LogD at pH=7.4 (distribution coefficient in octanol-water) for 22 drugs selected by Rekker et al. [2] were calculated by the ACD LogD algorithm. Experimental values are taken from different references [2-7].
Correlation statistics for the equation:
| Method |
b0 |
b1 |
R |
SD |
| ACD/LogD |
0.04±0.12 |
0.829±0.059 |
0.9531 |
0.39 |
Table: Observed and calculated values of logD at pH=7.4 for 22 drugs [1]. Method of calculation is the ACD algorithm.
| Name |
LogD at pH=7.4
(experimental)a) |
LogD at pH=7.4
(calculated) |
D |
| Atropine |
-0.44 |
-0.75 |
0.31 |
| Chloramphenicol |
1.00 [3] |
1.02 |
0.07 |
| Chlorothiazide |
-0.19 (pH=5) [4] |
-0.18b) (pH=5) |
-0.01 |
| Chlorpromazine |
3.15 [5] |
3.36 |
-0.21 |
| Cimetidine |
0.33 [6] |
0.21 |
0.12 |
| Diazepam |
2.8 [7] |
2.8 |
0.00 |
| Diltiazem |
1.29 [8] |
3.02 |
-1.73 |
| Diphenhydramine |
1.61 [9] |
2.29 |
-0.68 |
| Disopyramide |
0.38 [10] |
1.02 |
-0.64 |
| Flufenamic acid |
2.02 [11] |
2.03 |
-0.01 |
| Furosemide |
-0.92 [12] |
-0.99 |
0.07 |
| Haloperidol |
2.69 [13] |
2.94 |
-0.25 |
| Imipramine |
2.43 [14] |
2.41 |
0.02 |
| Lidocaine |
1.13 [15] |
1.20 |
-0.07 |
| Phenobarbital |
1.14 [16] |
1.51 |
-0.37 |
| Phenytoin |
2.29 [14] |
2.47 |
-0.18 |
| Procainamide |
-1.16 [17] |
-1.14 |
-0.02 |
| Propafenone |
0.01 (pH=5) [17] |
-0.07 (pH=5) |
0.08 |
| Propranolol |
1.2 [18] |
0.92 |
0.28 |
| Tetracaine |
2.34 [19] |
2.85 |
-0.51 |
| Trimethoprim |
0.64 [20] |
0.52 |
0.12 |
| Verapamil |
2.28 (pH=7) [21] |
2.99 (pH=7) |
-0.71 |
a) when the experimental logD at pH=7.4 was unknown, the
logD value nearest to 7.4 pH was used.
Figure: Dependence of logDexp vs logDcalc calculated by ACD/LogD for 22 drugs.
VII. LogP Example
The values of logP for 22 drugs selected by Rekker et al. [22] were calculated by ACD additive-constituitive method and compared with those obtained from the procedures of Rekker, Hansch and Leo and Moriguchi. Experimental values and calculated by these procedures are taken from [1].
Comparison of the reliabilities of Four Methods
Parameters are taken from the equation:
| Method |
a0 |
a1 |
R |
SD |
| ACD |
0.10 ± 0.22 |
0.882 ± 0.066 |
0.9481 |
0.50 |
| Hansch |
0.61 ± 0.20 |
0.868 ± 0.069 |
0.9430 |
0.53 |
| Rekker |
0.60 ± 0.24 |
0.754 ± 0.073 |
0.9183 |
0.63 |
| Moriguchi |
0.16 ± 0.37 |
1.09 ± 0.14 |
0.8635 |
0.80 |
Table 1. Observed and Calculated Values of logP for 22 Drugs [1]
| Name |
logPexp |
ACD |
D |
Hansch |
D |
Rekker |
D |
Moriguchi |
D |
| Atropine |
1.83 |
1.53 |
0.30 |
1.32 |
0.51 |
1.88 |
-0.05 |
2.21 |
-0.38 |
| Chloramphenicol |
1.14 |
1.02 |
0.12 |
0.69 |
0.45 |
0.32 |
0.82 |
1.23 |
-0.09 |
| Chlorothiazide |
-0.10 |
-0.03 |
-0.07 |
-1.24 |
1.14 |
-0.68 |
0.58 |
-0.36 |
0.26 |
| Chlorpromazine |
5.35 |
5.36 |
-0.01 |
5.20 |
0.15 |
5.10 |
0.25 |
3.77 |
1.58 |
| Cimetidine |
0.40 |
0.36 |
0.04 |
0.21 |
0.19 |
0.63 |
-0.23 |
0.82 |
-0.42 |
| Diazepam |
2.80 |
2.96 |
-0.16 |
3.32 |
-0.52 |
3.18 |
-0.38 |
3.36 |
-0.56 |
| Diltiazem |
2.70 |
4.53 |
-1.83 |
3.55 |
-0.85 |
4.53 |
-1.83 |
2.67 |
0.03 |
| Diphenhydramine |
3.27 |
3.66 |
-0.39 |
2.93 |
0.34 |
3.41 |
-0.14 |
3.26 |
0.01 |
| Disopyramide |
2.58 |
2.86 |
-0.28 |
1.35 |
1.23 |
2.57 |
0.01 |
2.47 |
0.11 |
| Flufenamic acid |
5.25 |
5.62 |
-0.37 |
5.58 |
-0.33 |
5.81 |
-0.56 |
3.86 |
1.39 |
| Furosemide |
2.03a) |
2.92 |
-0.89 |
2.04 |
-0.01 |
1.38 |
0.65 |
0.43 |
1.60 |
| Haloperidol |
3.36 |
4.06 |
-0.70 |
3.52 |
-0.16 |
3.57 |
-0.21 |
4.01 |
-0.65 |
| Imipramine |
4.80 |
4.47 |
0.33 |
4.41 |
0.39 |
4.43 |
0.37 |
3.88 |
0.92 |
| Lidocaine |
2.26 |
2.36 |
-0.10 |
1.36 |
0.90 |
2.30 |
-0.04 |
2.52 |
-0.26 |
| Phenobarbital |
1.47 |
1.71 |
-0.24 |
1.37 |
0.10 |
1.23 |
0.24 |
0.78 |
0.69 |
| Phenytoin |
2.47 |
2.52 |
-0.05 |
2.09 |
0.38 |
2.76 |
-0.29 |
1.80 |
0.67 |
| Procainamide |
0.88 |
1.23 |
-0.35 |
1.11 |
-0.23 |
1.11 |
-0.23 |
1.72 |
-0.84 |
| Propafenone |
4.63 |
4.63 |
0.00 |
3.21 |
1.42 |
4.15 |
0.48 |
3.00 |
1.63 |
| Propranolol |
3.38b) |
3.10 |
0.46 |
2.75 |
0.81 |
3.46 |
0.10 |
2.53 |
1.03 |
| Tetracaine |
3.73 |
3.75 |
-0.02 |
3.65 |
0.08 |
3.55 |
0.18 |
2.64 |
1.09 |
| Trimethoprim |
0.91 |
0.79 |
0.12 |
0.66 |
0.25 |
-0.07 |
0.98 |
1.26 |
-0.35 |
| Verapamil |
3.79 |
5.03 |
-1.24 |
3.53 |
0.26 |
6.15 |
-2.36 |
3.23 |
0.56 |
a) in [1] the value -0.83 was presented (this value may be only at pH about
7.4). The corrected value was taken from [23]
Figure 1. Comparison of logPexp vs logPcalc calculated
by four different methods for 22 drugs [1].
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