微透析技术在口服和局部应用布洛芬后测定肌肉及皮下组织浓度中的应用。

Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration.

作者信息

Tegeder I, Muth-Selbach U, Lötsch J, Rüsing G, Oelkers R, Brune K, Meller S, Kelm G R, Sörgel F, Geisslinger G

机构信息

Department of Experimental and Clinical Pharmacology and Toxicology, University Erlangen/Nürnberg, Erlangen, Germany.

出版信息

Clin Pharmacol Ther. 1999 Apr;65(4):357-68. doi: 10.1016/S0009-9236(99)70128-1.

DOI:10.1016/S0009-9236(99)70128-1

PMID:10223771

Abstract

BACKGROUND

The topical administration of non-steroidal antiinflammatory drugs (NSAIDs) is widely used for the treatment of soft tissue pain. However, it is not known whether effective tissue concentrations are reached with the topical route.

OBJECTIVE

To evaluate and compare unbound muscle and subcutaneous tissue ibuprofen concentrations with use of microdialysis after topical and oral administration.

METHODS

In a 2-way crossover design, 11 healthy volunteers received either 800 mg oral ibuprofen or 16 g of 5% ibuprofen gel applied onto the skin of the thigh (defined area, 17 x 19 cm). Microdialysis catheters were inserted into the medial vastus muscle (25 to 30 mm) and into the subcutaneous adipose layer of the thigh (4 to 5 mm). Dialysate was collected in 20-minute intervals up to 5 hours.

RESULTS

Essentially all of the orally administered dose was recovered in urine as ibuprofen or metabolites during 24 hours, but only about 0.55% of the topically administered dose was recovered. The relative systemic bioavailability of ibuprofen gel, based on urine recovery data, was (mean +/- SD) 0.57%+/-0.30%. Mean values of the dialysate areas under the drug concentration-time curves after topical and oral administration were 731.2+/-605.0 and 176.6+/-122.9 ng x h x mL(-1) for subcutaneous tissue and 63.5+/-90.3 and 213.4+/-117.2 ng x h x mL(-1) for muscle, respectively. Muscle dialysate concentrations after topical administration varied considerably among the subjects.

CONCLUSION

These results suggest that, if target tissue concentrations correlate directly with the degree of pain relief, patients with pain caused by dermal or subcutaneous tissue damage will have greater pain relief after topical administration of ibuprofen accompanied with less systemic side effects. In addition, a proportion of patients with muscle pain may also experience pain relief from topical ibuprofen.

摘要

背景

非甾体抗炎药（NSAIDs）的局部给药广泛用于治疗软组织疼痛。然而，尚不清楚局部给药途径是否能达到有效的组织浓度。

目的

通过微透析评估和比较局部和口服给药后未结合的肌肉和皮下组织中布洛芬的浓度。

方法

采用两交叉设计，11名健康志愿者分别口服800mg布洛芬或在大腿皮肤（规定面积，17×19cm）涂抹16g 5%布洛芬凝胶。将微透析导管插入股内侧肌（25至30mm）和大腿皮下脂肪层（4至5mm）。每隔20分钟收集一次透析液，共收集5小时。

结果

口服给药剂量在24小时内基本上全部以布洛芬或代谢物形式在尿液中回收，但局部给药剂量仅回收约0.55%。根据尿液回收数据，布洛芬凝胶的相对全身生物利用度为（均值±标准差）0.57%±0.30%。局部和口服给药后皮下组织药物浓度-时间曲线下透析液面积的均值分别为731.2±605.0和176.6±122.9ng·h·mL⁻¹，肌肉的均值分别为63.5±90.3和2⒈4±117.2ng·h·mL⁻¹。局部给药后肌肉透析液浓度在受试者之间差异很大。