Influence of methodological aspects on tissue drug concentration estimation.
Fundamental studies in tissue drug extraction have been made using rokitamycin as a test probe. Radiolabelled rokitamycin was administered intravenously to 12 rats. Lungs and femurs were excised a few minutes later. Rokitamycin was extracted from lungs using six procedures (based either on ion-pairing, dissolution or deproteinization) whose performances (mean recovery and reproducibility) were compared. Three grinding procedures were also compared for the extraction of rokitamycin from bone: pulverization by a magnetic stirring bar in a liquid nitrogen bath, slicing into small pieces and crushing with pestle and mortar. The effect of binding proteins (albumin or alpha 1-acid glycoprotein) in the extraction mixture was also evaluated. Magnetic stirring bar grinding was the most efficient. Deproteinization was necessary to obtain the highest recovery, but the agent had to be chosen carefully. Binding proteins either had no effect or decreased the recovery of rokitamycin. Recovery from bone was lower than that from lung. Binding to cellular components in the post-extraction pellet was only 3% (lung) and 9% (bone). It is concluded that a careful optimization of the extraction procedure of a drug from a tissue allows quantitative and reproducible measurement of its concentration.
Petitjean
O
O
Département de Pharmacotoxicologie, Hôpital Avicenne, Bobigny, France.
Tod
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M
Louchahi
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K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis*; D001842:Bone and Bones / Q000737:chemistry*; D002250:Carbon Radioisotopes; D055598:Chemical Phenomena; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D002627:Chemistry, Physical; D008168:Lung / Q000737:chemistry*; D008297:Male; D015644:Miocamycin / Q000031:analogs & derivatives* / Q000032:analysis; D051381:Rats
D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D015644:Miocamycin; C033383:rokitamycin