Alizapride Research Articles

β-cyclodextrin-enhanced Spectrofluorometric Methods for the Determination of Substituted Benzamides (Itopride Hydrochloride, Alizapride, and Mosapride Citrate) in Pharmaceutical Preparations

Two spectrofluorometric methods are developed and optimized for the determination of substituted benz amides, namely itopride hydrochloride (ITO), alizapride (ALI), and mosapride citrate (MOS), in drug substances and pharmaceutical formulations. The first method is based on the measurement of the relative fluorescence intensity of the cited drugs in the absence of methyl-β-cyclodextrin at 380 ± 2 nm using an excitation wavelength of 310 nm in an aqueous solution. The linearity ranges were found to be 0.05–10, 0.1–10, and 0.1–10 μg/mL, with mean recoveries of 100.04% ± 0.21, 100.06% ± 0.65, and 100.08% ± 0.26 for ITO, ALI, and MOS, respectively. The second method is based on the significant enhancement of the fluorescence intensities of the drugs produced through complex formation with methyl-β-cyclodextrin in an aqueous solution at pH 6.6 in the case of ITO and pH 7.2 in the case of ALI and MOS. The fluorescence intensities of the formed complexes were measured at 420 ± 2 nm using an excitation wavelength of 310 nm. The linearity ranges were found to be 5–35, 3–15, and 2–30 ng/mL, with mean recoveries of 100.22 ± 30, 100.12 ± 0.24, and 100.30 ± 0.44, and limits of detection of 1.98, 1.32, and 0.66 ng/mL for ITO, ALI, and MOS, respectively. 1:1 stoichiometries for β -CD-drugs complexes were established. Association constants and Gibbs free energy were calculated by applying the Benesi–Hil de brand equation. The results were found to agree statistically with those obtained from the reference methods.

Long-term stability of dexamethasone and alizapride or ondansetron in sodium chloride 0.9% polyolefin bag at 5 ± 3 °C

The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C. Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend. The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r2) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days. The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.

Development and validation of a stability-indicating HPLC-UV method for the determination of alizapride and its degradation products

A stability-indicating high-performance liquid chromatography procedure has been developed for the determination of alizapride (AL) and its main degradation products alizapride carboxylic acid (AL-CA) and alizapride N-oxide (AL-NO2) in drug substance and product. The method was developed based on forced degradation data obtained by HPLC–MS analysis. Indeed AL underwent chemical degradation by acid/base catalyzed hydrolysis and oxidation the main degradation products being AL-CA and AL-NO2 respectively. The separation and quantisation were achieved on a 150-mm reverse phase column with a hydrophilic linkage between silica particles and hydrophobic alkyl chains. The mobile phase was constituted (flow rate 1.5 mL min −1) of eluant A: aqueous acetate buffer (pH 4.0; 20 mM) and eluant B: CH 3OH using a gradient elution and detection of analytes at 225 nm. The method showed good linearity for the AL, AL-CA, AL-NO2 mixture in the 25–75, 1–15 and 1–15 μg mL −1 ranges respectively, being all the square of the correlation coefficients greater than 0.999. The precision, determined in terms of intra-day and inter-day precisions and expressed as RSDs were 0.8, 1.3 and 2.1% and 1.0, 1.7, 4.8% for AL, AL-CA and AL-NO2 respectively. The method demonstrated also to be accurate; indeed the average recoveries, at 100% and 0.2% of the target assay concentration, were 100.5, 98.6, and 96.8% for AL, AL-CA and AL-NO2 respectively. The robustness was also evaluated by variations of mobile phase composition and pH. Finally, the applicability of the method was evaluated in commercial dosage form analysis as well as in stability studies.

Comparative Effects of Intravenously Administered Alizapride and Prochlorperazine in Cisplatin-Induced Emesis

Comparative Effects of Intravenously Administered Alizapride and Prochlorperazine in Cisplatin-Induced Emesis

1232 Clinical and economical efficacy from a new decision tree for the use of antiemetic treatments

Since 1993, by way of controlling the cost of the antiemetics used in our institution, we have established two consecutive decision trees. A new tree based on our results with the first one (5th Int Congress Anti Cancer Chemot, Paris, 1995, abstr 445) and on the last literature data was used from 02–1994 to 01–1995. All patients treated by chemotherapy (CT) were concerned. We report the results from 9 months of applying. The study concerned clinical efficacy, respect of the decision tree and cost of the antiemetics. Treatment (tmt). There were 4 groups corresponding to various emetic situations, with a progression in the use of 9 different schemes for cycle tmt (0,F,G,H,II ,I2,J,K,L), and 3 schemes for postcycle tmt (X,Y,Z). Failure of a scheme was defined by a number of emetic events ≥ 2/day. In this case the scheme was changed at the next cycle for the following one. Group 1: no emetic CT (ex: vinorelbine): 0: no tmt; F: alizapride (ALZ) 100 mg IV; no pre and post tmt. Group 2: moderately emetic CT (ex: FEC-FAC): G: alz 100 mg IV hour (H) 0 and H4, methylprednisolone (MP) 120 mg IV HO; H: ondansetron (ond) 8 mg IV H0, MP 120 mg H0; pre and post tmt. Group 3: CT on several days (ex:BEP): 11: Dl granisetron (gra) 3 mg IV H0, MP 120 mg IV H0- D2 to D5 alz 100 mg IV H0 and H4, MP 120 mg IV H0; 12: 11 plus chlorazepate 20 mg IV; J: ond 8 mg IV H0 Dl to D5, MP 120 mg IV H0 Dl to D5; L: chlorpromazine IV 5 mg/sqm/3x/D; pre and post tmt. Group 4: highly emetic CT (ex: cisplatine >70 mg/m2): K: gra 3 mg IV H0, MP 120 mg IV H0; L; pre and post tmt. Precycle tmt: alprazolam (ALP) 0.25 mg PO 3x/D D-3 to D-1. Post cycle TMT for 3 days with 3 schemes. X: metoclopramide 20 mg PO 3x/D, MP 16 mg PO 3x/D. Y: X plus alp 0.25 mg PO 3x/D. Z: ond 8 mg PO x3/D. Results Group 1: for 1836 cycles of CT; 0: 92.27%, F:7.3%, G to K: 0.43%; X + Y: 6%. Group 2: for 893 cycles of CT; G: 66.41%, H: 28.22%, I1 to L: 5.37%; X: 82.75%, Y + Z: 8.7%. Group 3: for 166 cycles of CT; 11: 78.92%, 12: 5.42%, J: 3.01%, K: 7.83%, others: 4.62%; X: 82.5%, Y+ Z: 6%. Group 4: for 163 cycles of CT; K: 96.93%, others: 3.07%; X: 81.1%, Y + Z: 2.4%. There were 2.6% of mistakes. The decision tree is suitable, with clinical results considered as satisfactory. The cost of treatments has been reduced by a half since the utilization of the decision trees, in spite of an increase in the number of patients.

Dexamethasone plus Ondansetron versus Dexamethasone plus Alizapride in the Prevention of Emesis Induced by Cisplatin- Containing Chemotherapies for Urological Cancers

Thirty-six consecutive patients, who were to be treated with cisplatin-based chemotherapy for testicular or bladder cancer, underwent a single-blind randomized study to compare the antiemetic therapies with dexamethasone (DEX)+ondansetron (OND) and DEX + alizapride (ALI). Eighteen patients were assigned to each arm. DEX, 20 mg in 100 ml saline was administered i.v. 30 min prior to cisplatin, OND, 8 mg, or ALI, 100 mg in 100 ml saline were administered i.v. 15 min prior to cisplatin and repeated 4 and eventually 8 h later. Chemotherapy regimens contained cisplatin 25 mg/m2 for 4 consecutive days to be repeated for 4 courses every 4 weeks. During the first course a complete emetic control was observed in 15 (83%) and partial in 3 of the 18 patients treated with DEX + OND versus only 2 complete and 7 partial responses and 9 (50%) failures among the 18 patients treated with DEX + ALI. Thirty-one patients were evaluable for 4 courses of therapy. Complete emetic control was achieved in 11 (69%) and partial in 5 (31%) among the 16 patients treated with DEX + OND, versus only 1 (7%) partial response and 14 (93%) failures among the 15 treated with DEX + ALI (p < 0.001). Furthermore, DEX + OND gave a complete antiemetic control in 13 out of 14 patients who had failed DEX + ALI. Delayed vomiting was observed in 4 (22%) of 18 patients primarily treated with DEX + OND and in 1 (7%) of the 15 patients subsequently treated. Constipation and headache occurred more frequently among patients treated with DEX + OND, but there was no significant difference with DEX + ALI. Hiccup was significantly more frequent among patients treated with DEX + ALI.(ABSTRACT TRUNCATED AT 250 WORDS)