title: Therapeutic drug monitoring in interstitial fluid: a feasibility study using a comprehensive panel of drugs.
abstract: This study compared drug concentration-time profiles in interstitial fluid (ISF) and blood, using an established animal model and a comprehensive panel of drugs, to examine the feasibility of therapeutic drug monitoring (TDM) in ISF. An intravenous bolus of vancomycin, gentamicin, tacrolimus, cyclosporine, mycophenolate, valproic acid, phenobarbital, phenytoin, carboplatin, cisplatin, methotrexate, theophylline, or digoxin was administered into the ear vein (n = 4-6) of rabbits. Serial (0-72 h after dose) blood and ISF concentrations (collected via an ultrafiltration probe) were determined by validated analytical assays. Pharmacokinetic parameters were generated by noncompartmental analysis. Vancomycin, gentamicin, and carboplatin showed no significant difference in area under the curve (AUC) values in ISF and blood, respectively. Other AUCs were lower (mycophenolic acid, valproic acid, phenobarbital, cisplatin, methotrexate, theophylline, and digoxin) or not measurable (tacrolimus, cyclosporine, and phenytoin) in ISF with our extraction technique. Similar concentration-time profiles in the two matrices were evident for a selection of drugs tested. Using a comprehensive panel of drugs in a single experimental setting, we have identified agents that can be quantified in ISF. Our newly developed scoring algorithm can help determine the feasibility of conducting TDM in ISF.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tony K L
authors.initials: TK
authors.lastname: Kiang
authors.forename: Veronika
authors.initials: V
authors.lastname: Schmitt
authors.forename: Mary H H
authors.initials: MH
authors.lastname: Ensom
authors.forename: Beverly
authors.initials: B
authors.lastname: Chua
authors.forename: Urs O
authors.initials: UO
authors.lastname: Häfeli
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D045604:Extracellular Fluid / Q000378:metabolism*; D005240:Feasibility Studies; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D000970:Antineoplastic Agents; D001993:Bronchodilator Agents; D007166:Immunosuppressive Agents