| 2 | Pharmacokinetics | Zou et al.
| 2008
| Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study
| Crossover randomized open-label bioequivalence study | 24
| 23.5 (22-30) | Healthy males
| CPH | Oral
(capsules vs tablets) | 200 mg after 12h overnight fast | Single dose 1 week washout | After oral administration, CPH is absorbed from the GI tract and hydrolyzed into chlorophenoxyacetic acid. As a prodrug, CPH is not detected in plasma. Pharmacokinetic properties of chlorophenoxyacetic after 2 oral formulations of generic CPH hydrochloride administration: Cmax of the test and reference formulation: 12.6±2.8 and 12.8±3.0 μg/mL, respectively. Tmax of the test and reference formulation: 2.1±0.4 and 2.0±0.3 h. T1/2 of the test and reference formulation: 5.8±2.7 and 6.0±2.1 h. AUC 0-24 of the test and reference formulations: 34.1±7.9 and 34.2±8.1 μg/mL/h.
Compared with the reference tablet formulation, the CPH hydrochloride capsule (test) formulation had no statistically significant differences in bioavailability (p>0.05; Power =0.99) and no period or sequence effects were observed for any pharmacokinetic property.
| CPH hydrochloride was well tolerated by all the volunteers. No AEs were reported by subjects or found on analysis of vital signs or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis). AEs associated with CPH hydrochloride (eg, excitement, insomnia, lassitude, headache) were not reported during the study or 1 week after the study.
| The authors would like to thank JianMa Pharmaceutical Corporation for providing the capsule formulation of CPH hydrochloride, including the 4-chlorophenoxyacetic acid and CPH hydrochloride reference standards used in this research |
| 3 | Psychiatry & psychology | Popa et al.
| 1994
| Antagonic-stress superiority versus meclofenoxate in gerontopsychiatry (alzheimer type dementia)
| Parallel DB-randomized comparative trial | 63 CPH: 31
Antagonic- Stress: 32
| | Elderly with mild to moderate senile dementia
| CPH (Sintofarm, Bucharest, Romania) | Oral
(capsules:
2 gastrosoluble and 1 enterosoluble with lactose) | 1560 mg/day
(260 mg x2=520 mg, before each meal) "A total MF dose of 1520 mg/day" (mistake)
| 3 months | Degrees of improvements (reduction of geriatric psychopathology and recovery of cognitive functions) were significant in both treatments (final vs. baselines): for AS p<0.001 and for MF from p<0.01 to 0.001, indicating the utility of these neurometabolic nootropics in prolonged treatment of senile dementia of Alzheimer type. Final comparisons between treatments evidenced the superiority of AS vs. MF on SCAG (Sandoz Clinical Assessment-Geriatric) and SASG (Self-Assessment Scale-Geriatric) (p<0.05, 0.01 or 0.001). The intensity of geriatric psychopathology assessed by SCAG (1 severity interval=18) was reduced in total score, from the superior limit of mild to moderate (72 - 54 level) to mild (54 - 36 interval), by AS from 71.2±7.7 to 46.1±6.5 (-35.3%) vs. MF from 68.3±7.2 to 52.0±7.6 (-23.9%).
The reductions of the scores in SCAG I-V subscales listed were:
AS (from pre to post) vs. MF (from pre to post) Cognitive dysfunction: -32.7% (from 15.3±2.5 to 10.3±1.9) vs. -26.1% (15.3±1.9 to 11.3±2.6)
Interpersonal relationships: -38.7% (from 16.8±3.2 to 10.3±2.0) vs. -23.3% (15.9±2.3 to 12.2±2.5)
Affective disorders: -40% (from 14.0±2.1 to 8.4±1.5) vs. -28.4% (12.7±2.3 to 9.1±1.6)
Apathy: -26.7% (from 13.1±2.7 to 9.6±1.7) vs. -18.5% (13.0±1.9 to 10.6±2.0)
Somatic dysfunction: -37% (from 11.9±1.8 to 7.5±1.3) vs. -23% (11.3±2.3 to 8.7±1.9)
Symptom frequency autoevaluated by SASG (same variables as SCAG) also decreased, from the superior limit of mild to moderate to mild interval, by AS with 21.1 (-30.9%) vs. MF with 14.1 (-20.9%). The reductions of the scores in SASG I-V subscales were:
AS (from pre to post) vs. MF (from pre to post) Cognitive dysfunction: -29.3% (from 15.7±2.5 to 11.1±2.0) vs. -23.7%(15.2±3.0 to 11.6±2.8)
Interpersonal relationships: -34.6% (from 16.2±3.3 to 10.6±2.1) vs. -18.9% (14.8±2.0 to 12.0±2.1)
Affective disorders: -34.7% (from 12.1±2.3 to 7.9±1.6) vs. -24.4% (13.1±2.3 to 9.9±2.0) Apathy: -22.2% (from 13.5±2.6 to 10.5±1.7) vs. -17.2% (12.8±2.4 to 10.6±2.2)
Somatic dysfunction: -34.5% (from 11.0±2.4 to 7.2±0.9) vs. -20% (11.5±2.5 to 9.2±2.1)
Recovery by nootropic treatments of attention-concentration evaluated by digit symbol increased 53.3% (from 7.5±1.6 to 11.5±2.4) by AS treatment (from weak baseline to medium final level) and 19.5% (from 8.2±1.4 to 9.8±1.6) by MF treatment (from medium baseline to medium final interval), meaning a more than 2.5-fold larger improvement by AS than by MF. Memory-learning restoration assessed by WMS (MQ) increased by 33.6% (from 81.3±9.8 to 108.6±11.4) in case of AS treatment (from the inferior limit of mild deficit, 81-90, to the upper level of medium memory, 91-110) and 22.1% (from 82.0±6.5 to 100.1±11.3) in case of MF treatment (from the inferior limit of mild deficit, up to the middle level of medium memory). The cognitive performance (general intelligence) evaluated by IQ of WAIS also improved by the two nootropica: the verbal, the performance, and the full IQ values increased by 16.8% (from 99.5±11.3 to 116.2±11.5), 26.4% (from 87.8±7.9 to 111.0±13.5) and 22.8% (from 93.0±8.4 to 114.2±11.9), respectively, in the AS treated groups, whereas the same improvements amounted to 9.1% (from 100.2±10.6 to 109.3±12.3), 10% (from 93.0±10.0 to 102.3±14.5) and 8% (from 97.1±7.9 to 104.9±12.6) in the MF treated patients. Again in this test AS was more efficient than the MF alone: more than 2.5-fold in the performance IQ and more than 2-7-fold in the full IQ. Accordingly, restoration of cognitive performance was also detected as shown by a reduction of the WAIS deterioration index by 56.5% (from 15.4±4.3 to 6.7±3.9) and 29% (from 13.8±4.4 to 9.8±4.1) in the AS and MF groups, respectively. Both nootropic a reduced mental impairment from the 19-10% range (possible deterioration) to the 9-0% level (nonsignificant impairment, or physiological deterioration), but the efficacy was more than 2.2 times higher with AS than with MF treatment.
|