Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Nasal Administration of Granisetron to Rats

흰쥐를 이용한 Granisetron함유 경비 투여제제의 평가 및 그 적용

  • Published : 2006.12.21
Download PDF
⟨ Previous Next ⟩

Abstract

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

Keywords

References

  1. C.-T. Huang, K.-C. Chen and T.-H. Tsai, Simultaneous measurement of blood and brain microdialysates of granisetron in rat by high-performance liquid chromato- graphy with fluorescence detection, J. Chromatogr. B, 716, 251-255 (1998) https://doi.org/10.1016/S0378-4347(98)00274-6
  2. G.J. Sanger and D.R. Nelson, Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron), Eur. J. Pharmacol., 159, 113-124 (1989) https://doi.org/10.1016/0014-2999(89)90695-X
  3. J.W. Upward, B.D. Arnold, C. Link, D.M. Pierce, A. Allen and T.C. Tasker, The clinical pharmacology of granisetron (BRL 43694), a novel specific 5-HT3 antagonist, Eur. J. Cancer, 26, S12-S15 (1990)
  4. J. Carmichael, B.M. Cantwell, C.M. Edwards, B.D. Zussman, S. Thompson, W.G. Rapeport and A.L. Harris, A pharma- cokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response, Cancer Chemother. Pharmacol., 24, 45-49 (1989)
  5. L.L. Brunton, J.S. Lazo and K.L. Parker, A Goodman & Gilman? The Pharmacological basis of Therapeutics, 11th ed., McGRAW-HILL Medical Publishing division. 1830-1831 (2006)
  6. C. Huang, R. Kimura, R Nasser and A.A. Hussain, Mechanism of nasal absorption of drugs I : physicochemical parameters influencing the rate of in-situ nasal absorption of drugs in rats, J. Pharm. Sci., 74, 608-611 (1985) https://doi.org/10.1002/jps.2600740605
  7. K.S.E. Su, K.M. Campanale and C.L. Gries, Nasal drug delivery system of a quaternary ammonium compound : clofilium tosylate, J. Pharm. Sci., 73, 1251-1254 (1984) https://doi.org/10.1002/jps.2600730915
  8. T. Sakane, M. Akizuki and M. Yoshida, Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity, J. Pharm. Pharmacol., 43, 449-451 (1990)
  9. T. Sakane, M. Akizuki, S. Yamashida, T. Nadia, M. Hashida and H. Sezaki, The transport of a drug to the cerebrospinal fluid directly from the nasal cavity : the relation to the lipiphilicity of the drug, Chem. Pharm. Bull., 39, 2456-2458 (1991) https://doi.org/10.1248/cpb.39.2456
  10. L. Illum, Nasal drug delivery: possibilities, problems and solutions, J. Control. Rel., 87, 187-198 (2003) https://doi.org/10.1016/S0168-3659(02)00363-2
  11. A.A. Hussain, A. Dakkuri and S. Itoh, Nasal absorption of ondansetron in rats : an alternative route of drug delivery, Cancer Chemother. Pharmacol., 45, 432-434 (2000) https://doi.org/10.1007/s002800051014
  12. A.A. Hussain, S. Hirai and R. Bawarshi, Nasal absorption of propranolol from different dosage forms by rats and dogs, J. Pharm. Sci., 69, 1411-1412 (1980) https://doi.org/10.1002/jps.2600691215
  13. International Conference on Harmonizaton, Note for Guidance on Validation of Analytical Procedures : Methodology, Committee for Proprietary Medical Products, CPMP/ICH/281/95, Approval 18 December 1996
  14. P. Dondeti, H. Zia and T.E. Needham, Bioadhesive and formulation parameters affecting nasal absorption, Int. J. Pharm., 127, 115-133 (1996) https://doi.org/10.1016/0378-5173(95)04115-X
  15. R.L. Smith, R.E. Smyth, B.D. Keck, G.O. Kinnett and C.A. Cruze, Effect of formulation and dosing variables on the intranasal absorption of loperamide in the rat, Pharm. Res., 9, S-207 (1992)