Nina M. van Sorge⁽¹⁾, JP Yska⁽²⁾, Hans Blansjaar⁽³⁾, Sandra Driessen⁽⁴⁾, Patricia Schepers⁽⁵⁾, Simon R. Bovenga⁽⁶⁾, A.A. van Sorge^{(7)
(1)(2)(3)(4)(5)(6)}Rijnstate Hospital - ARNHEM. Netherlands
⁽⁷⁾Rijnstate Hospital Arnhem - ARNHEM. Netherlands

	[Pharmacology]	[Orthopedics & Traumatology]

INTRODUCTION

Antibiotic impregnated acrylic bone cement (PMMA) beads and surgical cement are well accepted modalities in the treatment and prevention of infection after implantation of endoprostheses.

In the 60´s and early ´70´s the complication rate in total hip arthroplasties for postoperative infection was approximately 10%. By introducing strict aseptic techniques in the operating theatre, the introduction of pre- and peri-operative systemic antiobiotic prophylaxis and also the mixing of antibiotics with surgical cement reduced the infection level to less than 1%.

Early reports have appeared on the use and effectiveness of antibiotic impregnated bone cement ^(1,2).

We have undertaken an in vitro comparison of two bone cements loaded with the same antibiotic, gentamicin by use of two experimental settings; dynamic and non-dynamic time-elapsed leaching ⁽³⁾.

MATERIALS AND METHODS

Dynamic elution profile

To study the elution profile of the gentamicin loaded surgical cement we used a USP XXVI defined flow-through cell apparatus. The assembly consists of a 600 ml reservoir (fig.1) containing 250 ml buffered solution; a pump for the dissolution medium; a flow-through cell (fig 2); a waterbath that maintains the dissolution medium at 37 ± 0,5 °C, a device for automatic sampling of the eluate.

Flow rate of the dissolution medium: 84 ml/hr.

Dissolution medium: buffered phosphate solution pH 7,5 ± 0,1 (KH₂PO₄ 1.82 g/l; Na₂HPO₄.2H₂O 9.5 g/l).

Specialties were obtained from Schering-Plough (Palacos®; Lotnr.:98D06-12/8928/97I09-46/2895) and Merck, Ortomed (Palamed®; Lotnr.: 8948 5054).

During the 190 min. test every 5 min. a sample of 250 uL was taken.

Non-dynamic time-elapsed elution profile

A final elution procedure (190 days) was studied by means of emersion of a sample of the gentamicin loaded cement in the same elution medium in an erlenmeyer (flask); appropriately diluted test samples were taken at four previously determined time points.

RESULTS

Results of gentamicin release from both Palacos® and Palamed® using the USP XXIV flow-through cell apparatus are presented in Table 1 and Fig.3.

Table 1
DYNAMIC ELUTION OF GENTAMICIN LOADED SURGICAL CEMENT DURING 190 MIN.

Specialties	n	Peak gentamicin level (mg/L); at 10 minutes	Mean gentamicin concentration from 100 minutes (mg/L)	Percentage released
Palamed®	4	93,9 ± 16,2	5,73 ± 0,38	27,1
Palacos®	5	32,0 ± 10,7	1,78 ± 0,05	8,8

Fig.3

In the non-dynamic setting leaching of gentamicin from the bone cement was measured. Results of begin and end points are shown in table 2, whereas leaching characteristics of gentamicin during the whole time period are presented in fig.4.

Table 2
NON-DYNAMIC LEACHING OF GENTAMICIN LOADED SURGICAL CEMENT

Specialties	Gentamicin level after 3 days (mg/L)	Gentamicin level after 190 days (mg/L)	Percentage released after 190 days
Palamed®	1,67 ± 0,13	3,69 ± 0,25	69,9
Palacos®	0,64 ± 0,07	0.67 ± 0,06	13,3

DISCUSSION

Antibiotic impregnated acrylic bone cement (PMMA) beads and surgical cement are well accepted modalities in the treatment and prevention of infection after implantation of endoprostheses.

To obtain information on the elution profile of the included antibiotic from the bone cement, we studied the in vitro release of gentamicin from two marketed brands: Palacos® and Palamed®. Two experimental procedures, a dynamic and non-dynamic setting, were used. Several differences were noted between the two brands. First, the peak concentration of gentamicin was always higher for Palamed®. Second, the total amount of gentamicin released from the bone cement was higher for Palamed®, both in the dynamic and non-dynamic setting. Finally, in the non-dynamic experiment it became clear that leaching of gentamicin from Palacos® reached a steady-state condition, whereas from Palamed® leaching of gentamicin continued during the investigated time-period. This possibly resembles the difference in formulation between the two surgical cements. The clinical significance of the higher elution levels of gentamicin from the Palamed® will be subject of further research ^(4,5).

CONCLUSION

Gentamicin levels and peak concentrations are consistently higher with use of Palamed®. To interpretate these results in relation to clinical significance, further research will be necessary.

BIBLIOGRAPHY

Wahlig H, Hameister W, Grieben A Uber die freisetzung von gentamycin aus polymethylacrylat. I. Experimentelle untersuchungen in vitro Langenbecks Arch klin Chir 1972;331:169
Wahlig H, Dingeldein E Antibiotics and bonecements. Experimental and clinical long-term observations Acta Orthop Scand 1980;51:49
Dissolution testing of different dosage forms using the flowthrough method Pharm Ind 1983;45:617-22
Moore RD, Lietman PS, Smith CR Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration J Inf Dis 1987;155:93-9
Ortega A, Aldaz A, Giraldez J, Brugarolas, A Relationship between pharmacokinetic parameters of gentamicin and patient characteristics and/or clinical data in patients with solid organ tumors Pharmacy World & Science 1999;21:227-32

Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [MATERIALS AND METHODS] [RESULTS] [FIGURES] [DISCUSSION] [CONCLUSION] [BIBLIOGRAPHY] [PRESENTATION FILE] [Discussion Board]

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	[Pharmacology]	[Orthopedics & Traumatology]

Nina M. van Sorge, JP Yska, Hans Blansjaar, Sandra Driessen, Patricia Schepers, Simon R. Bovenga, A.A. van Sorge
Copyright © 1999-2000. All rights reserved.

Last update: 11/01/00