[Assessment of a Tiapride solution for its administration through continuous intravenous perfusion]. / Estudio de estabilidad de tiaprida en disolución para administración en perfusión intravenosa continua.

OBJECTIVES: Tiapride is a substituted benzamide classified as an atypical neuroleptic. To our knowledge, there are no published data on its stability prepared as a continuous intravenous infusion. The current study analysed its stability in two different infusion solutions and concentrations over 48 hours. METHOD: Triplicate samples of tiapride were prepared in 0.9% sodium chloride and in 5% dextrose solutions at final concentrations of 1 and 2 mg/ml. Samples were collected in glass bottles without photoprotection and at room temperature (25 ± 2 °C). Sampling times at 0, 1, 3, 6, 12, 24 and 48 hours included a visual inspection for colour changes and appearance of precipitation as well as pH determination. Tiapride was quantified at selected times by mass spectrometry using high-performance liquid chromatography. Concentration values in the samples corresponding to 0 hours were given a reference value of 100%. Concentrations in subsequent samples greater than 90% were considered stable. RESULTS: No colour change or precipitation was observed during the study period. pH values ranged between 0.1 and 0.4 units. At 48 hours, the concentration of remaining tiapride in sodium chloride 1 mg/ml and 2 mg/ml was 93.8% and 91.6%, respectively. That in 5% dextrose 1 mg/ml and 2 mg/ml was 96.8% and 94.1%, respectively. CONCLUSION: Dilutions of tiapride in 0.9% sodium chloride and in 5% dextrose solution, at concentrations of 1 mg/ml and 2 mg/ml, in glass bottles and at room temperature were stable both physically and chemically during 48 hours.

Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon.

Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon-induced mortality was observed after prophylactic administration of physostigmine (RR = 0.30) or the oxime K-27 (RR = 0.34); both treatments were significantly superior to the pre-treatment with all other tested compounds, including the established substance pyridostigmine. Tacrine (RR = 0.67), ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7-MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon-induced death, but to a lesser degree. Methylene blue, amiloride and metoclopramide had an unfavorable effect (RR ≥ 1), significantly increasing mortality. When CNS penetration by prophylactic is undesirable K-27 is a promising alternative to pyridostigmine.