Figure 1.
Intestinal absorption, calculated values of polar surface area, volume, molecular weight, acidity descriptors (pKa values for pH = 7_4) for investigated antipsychotic drugs
| No. | Compound | % ABS | PSA | Vol | Mw | pKa |
|---|---|---|---|---|---|---|
| 1 | Chloropromazine | 10–80* | 8.17 | 285 | 319 | 9.20 |
| 2 | Flupentixol | 47 | 26.70 | 379 | 435 | 8.51 |
| 3 | Haloperidol | 65 | 40.54 | 337 | 376 | 8.05 |
| 4 | Zuclopenthixol | 49 | 26.70 | 361 | 401 | 8.43 |
| 5 | Aripiprazole | 87 | 44.81 | 395 | 448 | 7.46 |
| 6 | Clozapine | 65 | 35.16 | 292 | 327 | 7.50 |
| 7 | Olanzapine | 87 | 35.16 | 286 | 312 | 7.24 |
| 8 | Quetriapine | 100 | 48.83 | 352 | 384 | 7.06 |
| 9 | Risperidone | 70 | 64.17 | 374 | 410 | 8.76 |
| 10 | Sertindole | 75 | 40.41 | 390 | 441 | 8.59 |
| 11 | Ziprasidone | 60 | 48.47 | 352 | 413 | 7.09 |
_ The antipsychotic drugs intestinal absorption data collected from literature (*) and predicted using (A) XlogP and Vol data; (B) XlogP2 and Mw; (C) XlogP and pKa values
| No. | Compound | ABS%(*) | ABS% (A) | ABS% (B) | ABS% (C) |
|---|---|---|---|---|---|
| 1 | Chloropromazine | 50* | 37 | 37 | 71 |
| 2 | Flupentixol | 47 | 71 | 74 | 67 |
| 3 | Haloperidol | 65 | 63 | 62 | 66 |
| 4 | Zuclopenthixol | 49 | 69 | 68 | 70 |
| 5 | Aripiprazole | 87 | 76 | 77 | 52 |
| 6 | Clozapine | 65 | 52 | 51 | 61 |
| 7 | Olanzapine | 87 | 65 | 62 | 74 |
| 8 | Quetriapine | 100 | 80 | 76 | 66 |
| 9 | Risperidone | 70 | 84 | 81 | 87 |
| 10 | Sertindole | 75 | 78 | 79 | 72 |
| 11 | Ziprasidone | 60 | 70 | 75 | 55 |
Drug - like properties of investigated antipsychotic drugs
| Lipophilicity descriptor (XlogP2) | 2.32 – 4.92 |
| Aqueous solubility (logS) | (−5.78) – (−3.22) |
| Acidity descriptor (pKa) | 7.06 – 9.20 |
| Polar surface area (PSA, Å2) | 8.17 – 64.17 |
| Molecular weight (Mw) | 312 – 448 |
| Volume value | 285 – 395 |
| Percent of oral absorption (%ABS) | 10 – 100 |
The lipophilicity (logP) and solubility (logS) values of investigated antipsychotic drugs
| No. | Compound | logP exp | ClogP | AlogPs | AClogP | milogP | AlogP | MlogP | XlogP2 | XlogP3 | logS |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Chloropromazine | 5.41 | 5.80 | 5.18 | 5.03 | 5.03 | 4.74 | 3.77 | 4.92 | 5.19 | −4.84 |
| 2 | Flupentixol | 4.51 | 4.34 | 4.56 | 4.45 | 4.91 | 4.82 | 3.89 | 4.42 | 4.51 | −4.50 |
| 3 | Haloperidol | 4.30 | 3.85 | 3.70 | 4.63 | 4.30 | 3.89 | 4.01 | 3.98 | 3.23 | −4.81 |
| 4 | Zuclopenthixol | nd | 4.13 | 4.46 | 4.30 | 4.69 | 4.54 | 3.58 | 4.12 | 4.31 | −4.55 |
| 5 | Aripiprazole | 4.50 | 4.63 | 5.21 | 4.58 | 5.08 | 5.00 | 3.61 | 4.49 | 4.64 | −4.95 |
| 6 | Clozapine | 3.23 | 4.10 | 3.67 | 3.21 | 4.14 | 3.95 | 2.96 | 3.74 | 3.08 | −3.26 |
| 7 | Olanzapine | 2.00 | 3.40 | 3.61 | 2.98 | 3.47 | 3.21 | 2.31 | 2.32 | 2.86 | −3.28 |
| 8 | Quetriapine | 2.80 | 3.37 | 2.93 | 2.80 | 3.49 | 3.18 | 2.36 | 2.83 | 2.14 | −3.22 |
| 9 | Risperidone | 2.50 | 2.71 | 2.41 | 3.37 | 2.96 | 3.32 | 3.61 | 3.07 | 2.72 | −3.89 |
| 10 | Sertindole | nd* | 5.07 | 4.29 | 4.52 | 3.84 | 4.68 | 3.77 | 4.10 | 4.07 | −5.78 |
| 11 | Ziprasidone | 3.80 | 3.58 | 4.64 | 2.45 | 4.05 | 4.26 | 3.44 | 3.77 | 4.02 | −4.32 |
Intercorrelations between different logP values of investigated antipsychotic drugs
| logP exp | ClogP | AlogPs | AClogP | milogP | AlogP | MlogP | XlogP2 | XlogP3 | |
|---|---|---|---|---|---|---|---|---|---|
| logP exp | 1 | ||||||||
| ClogP | 0.8548 | 1 | |||||||
| AlogPs | 0.8062 | 0.8297 | 1 | ||||||
| AClogP | 0.7897 | 0.7331 | 0.5279 | 1 | |||||
| milogP | 0.9099 | 0.8913 | 0.9080 | 0.7504 | 1 | ||||
| AlogP | 0.8861 | 0.7914 | 0.9067 | 0.6666 | 0.9418 | 1 | |||
| MlogP | 0.7545 | 0.4027 | 0.4322 | 0.7107 | 0.5626 | 0.6745 | 1 | ||
| XlogP2 | 0.9704 | 0.8353 | 0.7882 | 0.7741 | 0.9065 | 0.9296 | 0.7891 | 1 | |
| XlogP3 | 0.8693 | 0.8369 | 0.9275 | 0.6699 | 0.8812 | 0.9426 | 0.6495 | 0.8822 | 1 |