Table 3 provides a summary of carboplatin doses administered and carboplatin clearance values observed on course 1 (nine patients), courses 1 and 2 (six patients) and courses 1 3 (two patients).
The values observed were particularly apparent when STX243 was administered orally, with clearance values above 700 ml kg−1 h−1 and volumes of distribution above 12 l kg−1 for both doses under investigation.
In a single agent phase I study in 23 patients (Graham et al, 1992), where losoxantrone dose ranging from 5 55 mg m−2 was administered, the plasma clearance averaged 417±194 ml min m−2.
Pharmacodynamic studies have been performed to predict the clearance and administer the appropriate dose of carboplatin in individual patients (Egorin et al, 1985; Calvert et al, 1989; Chatelut et al, 1995; Duffull and Robinson, 1997; Mountain and Dresler, 1997).
However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles.
Intra-articular IL1Ra delivery did not result in marked improvement for this model; this may be driven by rapid clearance of administered IL1Ra from the joint space.
No cisplatin was administered if the creatinine clearance level was less than 30 ml min−1.
When considering the excretion of any agent administered systemically, the renal clearance is the critical determinant of pharmacokinetics.
The treatment with HE2000 also resulted in lower percentages of lungs involved in pneumonia and higher bacterial clearance, when administered as an adjunct to conventional chemotherapy [ 25].
However, patients with severe renal impairment had a shorter OS. 87 With dosing of lenalidomide being administered according to creatinine clearance (Table 4), toxicity of lenalidomide was independent of renal function.
46 In patients with underlying kidney disease at baseline, tenofovir can still be administered if the creatinine clearance is greater than 10 mL/min or if they are receiving hemodialysis.
