A-1670. Pharmacokinetics of Three Different Dosing Regimens of Colistin with Meaning for Optimum Use
Session: Slide Session: Colistin Pharmacokinetics/Dynamics
Sunday, October 26, 2008: 12:00 AM
Room: Constitution B (Grand Hyatt)
Background: Colistin has been used extensively in critically ill patients, its pharmacokinetics (Pk), however, have not been fully elucidated and the optimal dosing regimen has not been defined. In the present study, we examined the Pk of three different dosing regimens of colistin methanesulphonate (CMS). Methods: Adult patients with normal kidney function who had purulent bronchitis caused by Pseudomonas aeruginosa were treated with CMS monotherapy. Four patients received 3 million units (MU) q8 h, four 4.5 MU q12 h, and five 9 MU q 24 h intravenously. Blood samples were collected on the third day of treatment at 0, 1, 2, 4, 8, 12 and 24 h following drug infusion. CMS and colistin levels were determined by HPLC. Susceptibilities to colistin were determined by Etest. P. aeruginosa ATCC 27853 (MIC 1.5mg/L) was used as a control strain. Results: Seven patients were male and 6 female, their mean age, body weight and creatinine clearance were 61 years, 77 Kg, and 84 mL/min respectively. The Pk parameters according to the treatment regimen are shown in the table.
ParametersSubstanceTreatment regimens
3MU q 8h4.5 MU q 12h9 MU q 24h
AUC (mg.h/L)CMS
Colistin
12.38±2.41
11.42±1.91
13.34±3.05
13.70±2.27
23.48±3.72
22.43±3.88
t1/2 (h)CMS
Colistin
8.3±1.3
7.8±1.7
9.2±1.4
8.8±1.6
11.4±1.5
9.6±1.4
Cmax (mg/L)CMS
Colistin
4.38±1.56
3.34±0.89
4.75±1.37
2.98±0.74
8.23±2.58
5.63±1.97
Cmin (mg/L)CMS
Colistin
2.66±0.79
2.07±0.38
3.43±1.12
1.64±0.53
2.63±0.88
2.61±0.84
Vd (L)CMS
Colistin
124.7±16.8
142.4±31.8
135.8±20.7
118.8±23.2
156.4±19.6
154.2±2.74

AUC: area under curve, t1/2: elimination half time, Vd: volume of distribution
The MICs of colistin for P. aeruginosa were ranging from 0.75 to 2 mg/L.
Conclusion: The once daily dosing of colistin results in higher Cmax / MIC ratio as compared to the other two regimens. These findings may have meaning for optimum clinical use.
Angelos Rigas1, Anna Skiada, MD2, Antonis Markoyannakis1, Christina Vafiadi1, Eirini Vafiadi1, George Petrikkos, MD, PhD3, George Thomopoulos1, George Daikos, MD4, JOHN Pavleas1, Konstantina Tzanetou1, Kostas Salatas1, Kostas Rigas1, Polys Tofas1 and  A. Skiada, None., (1)Laikon Hospital, University of Athens, (2)University of Athens, Athens, Greece, (3)4th Internal Medicine and Infectious Diseases Department, Attikon University General Hospital,Univ of Athens Med Sch, Athens, Greece, (4)Laikon General Hospital, Chaidari, Greece

Professor of Medicine in Medical School, University of Athens. Over 200 publications in peer reviewed journals. Specialist in infectious diseases.