Prospective use of optimal sampling theory: Steady‐state ciprofloxacin pharmacokinetics in critically ill trauma patients

We examined the use of optimal sampling theory to determine a sparse sampling design to estimate pharmacokinetic parameters of ciprofloxacin in patients who had sustained trauma. Two serum sampling strategies, consisting of six sampling times each, were derived on the basis of the patient's renal function (patients with creatinine clearance ≥ 6 L/hr/1.73 m2 and patients with creatinine clearances < 6 L/hr/1.73 m2). Two additional serum samples were obtained for other aspects to the study. A timed urine collection was also obtained. Pharmacokinetic parameter estimates were determined by comodeling the serum and urine data with a three‐compartment open model (parameterized as microconstants) with a bayesian algorithm and by noncompartmental analysis. Bayesian‐derived parameter estimates were total body clearance of drug from plasma, 29.8 L/hr/1.73 m2; renal clearance, 17.0 L/hr/1.73 m2; and nonrenal clearance, 12.7 L/hr/1.73 m2 and were not significantly different from noncompartmentally derived parameters (p = 0.80, p = 0.65 and p = 0.333, respectively). The study demonstrates the use of optimal sampling theory to determine an informative yet relatively sparse sampling strategy for a drug with a complex pharmacokinetic model.

[1]  A Forrest,et al.  A prospective evaluation of optimal sampling theory in the determination of the steady‐state pharmacokinetics of piperacillin in febrile neutropenic cancer patients , 1989, Clinical pharmacology and therapeutics.

[2]  G. Drusano,et al.  Pharmacokinetics of intravenously administered ciprofloxacin in patients with various degrees of renal function , 1987, Antimicrobial Agents and Chemotherapy.

[3]  A Schumitzky,et al.  A program package for simulation and parameter estimation in pharmacokinetic systems. , 1979, Computer programs in biomedicine.

[4]  R. Jelliffe,et al.  A computer program for estimation of creatinine clearance from unstable serum creatinine levels, age, sex, and weight , 1972 .

[5]  L B Sheiner,et al.  Population Pharmacokinetics of Procainamide from Routine Clinical Data , 1984, Clinical pharmacokinetics.

[6]  G. Drusano,et al.  Effect of saturable clearance during high-dose mezlocillin therapy , 1984, Antimicrobial Agents and Chemotherapy.

[7]  P. Blain,et al.  Steady-state Pharmacokinetics of Phenytoin from Routinely Collected Patient Data , 1983, Clinical pharmacokinetics.

[8]  G. Drusano,et al.  Dose ranging study and constant infusion evaluation of ciprofloxacin , 1986, Antimicrobial Agents and Chemotherapy.

[9]  A Forrest,et al.  An evaluation of optimal sampling strategy and adaptive study design , 1988, Clinical pharmacology and therapeutics.

[10]  G. Koren,et al.  Ethics of drug studies in infants: how many samples are required for accurate estimation of pharmacokinetic parameters in neonates? , 1987, The Journal of pediatrics.