One-compartment Method Research Articles

Pharmacokinetic characteristics of the triple inactivated plasma-derived Kedrion FIX concentrate: data from the KB037 clinical trial.

The pharmacokinetics data of phase I/II clinical trials (EudraCT Number: 2005-006186-14) of the new, triple inactivated plasma-derived Kedrion FIX concentrate was designed according to the recommendations of SSC-ISTH [1,2]: 11 post-infusion FIX/time points samples during the first 72 h. The PK data were also analysed by a modified, less dense, 9 FIX/time points, sample design. The outcomes of the safety and efficacy study and the pharmacokinetics' results have been previously and partially described [3,4]. The single-dose PK at enrolment (PK I) and the end of the trial (PK II) were analyzed by WinNonlin 7.0 (Pharsight) and according to three different methods: Non-Compartment Analysis (NCA), One Compartment Method (OCM), and Two-Compartment Method (TCM).The outcomes of PK parameters by TCM show that a higher number of FIX/time concentration points may not always give a better definition of the decay curve. On the other hand, the Terminal HL of NCA is deeply affected by the goodness of the last two-three points. The quite long Kedrion FIX HL may allow for a cost/effective tailoring of prophylaxis in haemophilia B patients.

Aminoglycoside Pharmacokinetic Parameters in Neurocritical Care Patients Undergoing Induced Hypothermia

To determine the effects of mild-to-moderate induced hypothermia-a neuroprotectant and/or therapeutic strategy for the management of intracranial hypertension in neurologically injured patients-on the pharmacokinetics of aminoglycoside therapy. Pharmacokinetic analysis. Critical care unit at a university-affiliated hospital. Three patients, aged 22, 24, and 47 years, who received tobramycin and had documented tobramycin levels while undergoing induced hypothermia for more than 24 hours for intracranial hypertension. For each of the three patients, predicted pharmacokinetic parameters (volume of distribution, first-order elimination rate constant, half-life, and renal drug clearance) based on population data were compared with their actual pharmacokinetic parameters that were calculated based on observed tobramycin serum levels. All three patients had a normal creatinine clearance, estimated according to established methods. When pharmacokinetic parameters were calculated after the first tobramycin dose using a one-compartment method, all patients had a slower first-order elimination rate and a larger volume of distribution compared with predicted population estimates. These findings suggest that induced hypothermia may result in impaired elimination of aminoglycosides. Caution should be exercised when attempting to use predicted pharmacokinetic parameters to dose aminoglycosides in this patient population, and first-dose pharmacokinetics should be considered to optimize the dose and dosing interval early in the course of therapy. Further investigation of this phenomenon with greater numbers of patients are needed to confirm these findings and to determine optimal dosing strategies of aminoglycosides in patients undergoing induced hypothermia.

General Purpose Antimicrobial Ophthalmic Solutions Evaluated Using New Pharmacokinetic Parameter of Maximum Drug Concentration in Aqueous

Purpose: In order to determine whether the one-component method for calculating drug concentration in the aqueous (AQC max) is useful for selecting an appropriate ophthalmic solution, six general purpose antimicrobial ophthalmic solutions already on the market were investigated. Methods: The drugs examined were levofloxacin (LVFX), chloramphenicol (CP), erythromycin lactobionate (EM), micronomicin sulfate (MCR), cefmenoxime hydrochloride (CMX), and disodium sulfobenzyl penicillin (SBPC). Fifty microliters of each solution was instilled into the cul-de-sac of New Zealand White rabbit eyes three times at 15-minute intervals. The drug concentrations in the aqueous humor 10, 30, 60, 120, and 240 minutes after the final instillation were examined by high performance liquid chromatography (HPLC) and/or bioassay. The AQC max was calculated using the one-compartment method. Results: The calculated AQC max was 2.5 μg/mL (HPLC method) and 2.28 μg/mL (bioassay method) for LVFX, 2.17 μg/mL for CP, and 0.45 μg/mL for EM. The AQC max for CMX, MCR, and SBPC could not be calculated by the one-compartment method. Conclusions: The AQC max of LVFX was higher than that of the two other general purpose antimicrobial ophthalmic solutions. The AQC max of these drugs might be a useful parameter for selecting an appropriate ophthalmic solution for the treatment of infected eyes.

Estimation of Glomerular Filtration Rate in Normal Sheep by the Disappearance of Iohexol from Serum

The aim of the study was to establish reference values for glomerular filtration rate (GFR) in healthy sheep from the clearance of iohexol in serum. Fifteen healthy sheep were tested twice with 14 to 21 days between tests. No side-effects were observed after iohexol injections and all the sheep were clinically normal during and after the study. The mean clearance of iohexol estimated by the two-compartment method was 1.8 ml/min per kg (95% CI = 1.6-2.0) in the first trial and 1.7 ml/min per kg (1.5-1.9) in the second trial. The mean GFRiohexol estimated by a one-compartment method was 1.9 ml/min per kg (1.7-2.2) in the first trial and 1.8 ml/min per kg (1.6-2.0) in the second. The GFR values were similar to those reported for the inulin method. The results indicate that the iohexol method is valid for estimating GFR in sheep, and it is easier to perform than the inulin method.