Absorption Kinetics of Subcutaneously Administered Ceftazidime in Hypoperfused Guinea Pigs

Overview

Journal Curr Ther Res Clin Exp

Specialty Pharmacology

Date 2015 Dec 10

PMID 26649076

Citations 1

Authors

Tsuyoshi Ebihara

Shinji Oshima

Mitsuyoshi Okita

Sayumi Shiina

Akio Negishi

Kousuke Ohara

Shigeru Ohshima

Hiroyuki Iwasaki

Akira Yoneyama

Eiji Kitazumi

Daisuke Kobayashi

Affiliations

Soon will be listed here.

Abstract

Background: Pneumonia is the most common cause of death in patients with severe motor and intellectual disabilities (SMID), and intravenous ceftazidime (CAZ) is a widely used treatment for such infections. However, intravenous administration in patients with SMID may be difficult because of insufficient vascular development.

Objectives: The aim of our study was to determine the feasibility of subcutaneous drug administration by mentholated warm compresses (WMCs) as an alternative delivery method for ceftazidime in patients with SMID.

Methods: CAZ was subcutaneously administered to the abdominal region of naphazoline-treated hypoperfused guinea pigs, which were used as a hemodynamic model of patients with SMID. MWCs or warm compresses (WCs) were applied to the injection site to increase blood flow. We calculated the cumulative CAZ absorption over time by using the deconvolution method.

Results: Application of MWCs or WCs increased blood flow at the administration site and increased CAZ plasma levels. Application of MWCs or WCs after subcutaneous CAZ injection led to higher CAZ plasma levels than the mutant prevention concentration for a longer period than was observed for CAZ administration without the application of MWCs or WCs.

Conclusions: The application of MWCs or WCs enhanced subcutaneous CAZ absorption by increasing blood flow. MWCs and WCs are considered to be safe and routine methods to induce defecation after surgery on the digestive system; thus, the combination of these methods and subcutaneous CAZ administration is a potential method for treating pneumonia in patients with SMID.

Citing Articles

A survey of subcutaneous blood flow in patients with SMID and subcutaneous ceftazidime administration using mentholated warm compresses in healthy subjects.

Ebihara T, Oshima S, Yasuda Y, Okita M, Ohara K, Negishi A J Int Med Res. 2016; 44(2):248-57.

PMID: 26912507 PMC: 5580067. DOI: 10.1177/0300060515625431.

References

Suzuki Y, Kobayashi M, Kuwabara K, Kawabe M, Kikuchi C, Fukuda M . Skin temperature responses to cold stress in patients with severe motor and intellectual disabilities. Brain Dev. 2012; 35(3):265-9. DOI: 10.1016/j.braindev.2012.04.003. View

Greiner J, Udell I . A comparison of the clinical efficacy of pheniramine maleate/naphazoline hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic solution in the conjunctival allergen challenge model. Clin Ther. 2005; 27(5):568-77. DOI: 10.1016/j.clinthera.2005.04.011. View

Teramoto S, Fukuchi Y, Sasaki H, Sato K, Sekizawa K, Matsuse T . High incidence of aspiration pneumonia in community- and hospital-acquired pneumonia in hospitalized patients: a multicenter, prospective study in Japan. J Am Geriatr Soc. 2008; 56(3):577-9. DOI: 10.1111/j.1532-5415.2008.01597.x. View

Brown E, Metcalf T, SLANETZ L . Visualization of the fate of injections of water-in-oil emulsions by means of radiopaque media, II. Ann Allergy. 1961; 19:1016-8. View

Hishinuma M, Hiramatsu N, Kasuga M, Ooyoshi M, Kaharu C, Misao H . [The effect on bowel sounds of very hot compresses applied to the lumbar region]. Nihon Kango Kagakkaishi. 1997; 17(1):32-9. DOI: 10.5630/jans1981.17.1_32. View

Pithavala Y, Soria I, Zimmerman C . Use of the deconvolution principle in the estimation of absorption and pre-systemic intestinal elimination of drugs. Drug Metab Dispos. 1997; 25(11):1260-5. View

Sato K, Oda T, Sugibayashi K, Morimoto Y . Estimation of blood concentration of drugs after topical application from in vitro skin permeation data. I. Prediction by convolution and confirmation by deconvolution. Chem Pharm Bull (Tokyo). 1988; 36(6):2232-8. DOI: 10.1248/cpb.36.2232. View

Takeda S, Nakai T, Wakai Y, Ikeda F, Hatano K . In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2006; 51(3):826-30. PMC: 1803152. DOI: 10.1128/AAC.00860-06. View

Yamaoka K, Tanigawara Y, Nakagawa T, Uno T . A pharmacokinetic analysis program (multi) for microcomputer. J Pharmacobiodyn. 1981; 4(11):879-85. DOI: 10.1248/bpb1978.4.879. View

10.

Yang T, Chan R, Kao C, Chiu J, Liu T, Kao N . Power spectrum analysis of heart rate variability for cerebral palsy patients. Am J Phys Med Rehabil. 2002; 81(5):350-4. DOI: 10.1097/00002060-200205000-00005. View

11.

Craig W . Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998; 26(1):1-10; quiz 11-2. DOI: 10.1086/516284. View

12.

Franchini M, Gandini G, De Gironcoli M, Vassanelli A, Borgna-Pignatti C, Aprili G . Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood. 2000; 95(9):2776-9. View

13.

Okada K, Yamaguchi T, Minowa K, Inoue N . The influence of hot pack therapy on the blood flow in masseter muscles. J Oral Rehabil. 2005; 32(7):480-6. DOI: 10.1111/j.1365-2842.2005.01448.x. View

14.

Henrichfreise B, Wiegand I, Luhmer-Becker I, Wiedemann B . Development of resistance in wild-type and hypermutable Pseudomonas aeruginosa strains exposed to clinical pharmacokinetic profiles of meropenem and ceftazidime simulated in vitro. Antimicrob Agents Chemother. 2007; 51(10):3642-9. PMC: 2043282. DOI: 10.1128/AAC.00160-07. View

15.

Veugelers R, Benninga M, Calis E, Willemsen S, Evenhuis H, Tibboel D . Prevalence and clinical presentation of constipation in children with severe generalized cerebral palsy. Dev Med Child Neurol. 2010; 52(9):e216-21. DOI: 10.1111/j.1469-8749.2010.03701.x. View

16.

Drlica K . The mutant selection window and antimicrobial resistance. J Antimicrob Chemother. 2003; 52(1):11-7. DOI: 10.1093/jac/dkg269. View

17.

Kobayashi D, Kawabata S, Sugibayashi K, Morimoto Y, Kimura M . In vitro/in vivo difference in enhanced skin permeation of nicardipine hydrochloride by the 1-menthol-ethanol system. Skin Pharmacol. 1996; 9(2):130-6. DOI: 10.1159/000211409. View

18.

Nakagawa T, Haginaka J, Yamaoka K, Uno T . High speed liquid chromatographic determination of cephalexin in human plasma and urine. J Antibiot (Tokyo). 1978; 31(8):769-75. DOI: 10.7164/antibiotics.31.769. View

19.

Borgna-Pignatti C, Franchini M, Gandini G, Vassanelli A, De Gironcoli M, Aprili G . Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload. Haematologica. 1998; 83(9):788-90. View

20.

Fukuda K, Nakagawa Y . [The relationship between the gross motor function and the causes of death in persons with severe motor and intellectual disabilities]. No To Hattatsu. 2013; 45(1):38-43. View