Alemón-Medina R, Rivera-Espinosa L, Zárate-Castañón P, Flores-Pérez C

Language: Spanish
References: 19
Page: 434-441
PDF size: 570.26 Kb.

ABSTRACT

Background: Eight out of ten patients in the Intensive Care Unit of the Instituto Nacional de Pediatría do not set the same anxiolytic and sedative effect using generic midazolam (PiSA^®) as with the innovative brand (Dormicum, Roche^®), although its bioavailability is 100%.
Objective: To determine significant differences in the sedative effect induced by generic and by innovative midazolam given parenterally.
Materials and methods: Randomised crossover study in 24 male Wistar rats allocated into 4 groups (n=6). Each individual was given a dose of 0.5 mg/kg intraperitoneally; sedation levels were determined by the scale of Salamone’s scale. Drug concentration in the vials of both brands was determined by high performance liquid chromatography (HPLC).
Results: The sedative effect of midazolam appeared at the same time for both groups and had the same duration regardless of the brand. The effect tends to be more durable with the innovative, but without statistical significance (ANOVA, p ≤ 0.05). Likely, most animals reached Salamone’s sedation level 3 with both brands.
Conclusion: Both innovative and generic midazolam brands provide the same level of sedative effect, which appears and lasts equally.

REFERENCES

1. Hartwig S, Roth B, Theisohn M. Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit. European Journal of Pediatrics 1991;150:784-788.

2. Lancel M, Crönlein T, Faulhaber J. Role of GABAA receptors in sleep regulation differential effects of muscimol and midazolam on sleep in rats. Neuropsychopharm 1996;15:63–74.

3. Katzung BG, Basic & Clinical Pharmacology, 10th edition, New York, USA, 1995; 1182.

4. Reves JG, Fragen RJ, Vinik HR, et al. Midazolam: pharmacology and use. Anesthesiology 1985;62:310-24.

5. Heizmann P, Eckert M, Ziegler WH. Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol 1983;16(Suppl 1):43S-49S.

6. NOM-062-ZOO-1999. Especificaciones técnicas para la producción, cuidado y uso de los animales de laboratorio. Diario Oficial de la Federación. México. 2001.

7. Chuck TL, McLaughlin PJ, Arizzi-LaFrance MN, Salamone JD, Correa M. Comparison between multiple behavioral effects of peripheral ethanol administration in rats: Sedation, ataxia, and bradykinesia. Life Sci 2006;79:154-161.

8. Flores-Pérez C, Chávez-Pacheco JL, Flores-Pérez J, Juárez- Olguín H, Ramírez-Mendiola B, García-Álvarez R, González- Zamora JF, Changin-Guerra A. Development and Validation of a Method to Quantify Midazolam in a New Oral Formulation for Pediatric Use. AJAC 2012;3:552-558.

9. Shelly MP, Mendel L, Park GR. Failure of critically ill patients to metabolize midazolam. Anaesth 1987;42:619-26.

10. Marriot P, Laasch HU, Wilbraham L, Marriot A, England RE, Martin DF. Conscious sedation for endoscopic and non-endoscopic interventional gastrointestinal procedures: meeting patients expectations, missing the standard. Clin Radiol 2004;59(2):180-185.

11. Bauer TM, Ritz R, Haberthür C, Ha HR, Hunkeler W, Sleight AJ, Scollo-Lavizzari G, Haefeli WE. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet 1995;345:145-47.

12. Vree TB, Shimoda M, Driessen JJ, et al. Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients. Clin Pharmacol Ther 1989;46:537-44.

13. Park GR, Miller E, Navapurkar V. What changes drug metabolism in critically ill patients? II. Serum inhibits the metabolism of midazolam in human microsomes. Anaesth 1996;51:11-15.

14. Malacrida R, Fritz ME, Suter PM, et al. Pharmacokinetics of midazolam administered by continuous intravenous infusion to intensive care patients. Crit Care Med 1992;20:1123-26.

15. Tobias JD. Sedation and analgesia in the Pediatric Intensive Care Unit. Pediatric Annals 2005;34(8):636-45.

16. Smith MT, Eadie MJ, O´Rourke Brophy T. The pharmacokinetics of midazolam in man. Eur J Clin Pharmacol 1981;19: 271-78.

17. Dundee JW, Halliday NJ, Harper KW, et al. Midazolam: a review of its pharmacological properties and therapeutic use. Drugs 1984;28:519-543.

18. Shenfield G, Gross A. The cytochrome P450 system and adverse drug reactions. Adv Drug React Bull 1999;194:739-42.

19. Serrano Espinosa VG. Estudio observacional del uso de midazolam genérico en el Instituto Oncológico Nacional de Panamá, para la sedación consciente en pacientes sometidos a gastroscopia. Barcelona, España. Mayo 2005.