Age-dependent cyclosporine: Pharmacokinetics in marrow transplant recipients

Abstract

We evaluated the effect of age on cyclosporine pharmacokinetics in 69 nonobese patients aged 10 months to 56 years (median 22 years) undergoing allogeneic bone marrow transplantation for treatment of aplastic anemia or hematologic malignancy. Cyclosporine pharmacokinetics were studied during the first 2 posttransplant weeks after an intravenous dose of 2.6 to 3.5 mg/kg. Serum cyclosporine concentrations were measured by HPLC. Cyclosporine concentration-time data were fitted to a two-compartment model with a nonlinear regression program. There was a significant inverse linear correlation between age and both total systemic clearance (CL) (r = 0.42; P less than 0.001) and volume of distribution at steady-state (Vss) (r = 0.33; P less than 0.01). Mean (+/- SE) cyclosporine CL was 82 +/- 21, 45 +/- 5, 38 +/- 9, 44 +/- 8, and 20 +/- 3 ml/min/kg and mean cyclosporine Vss was 34 +/- 11, 28 +/- 10, 15 +/- 4, 14 +/- 5, and 4.7 +/- 0.7 L/kg in patients 0 to 10 (n = 12), 11 to 20 (n = 19), 21 to 30 (n = 12), 31 to 40 (n = 17), and greater than 40 (n = 9) years old, respectively. Patients 0 to 10 years old had a significantly higher cyclosporine CL than those 11 to 40 or greater than 40 years old and also had a significantly larger Vss than those greater than 40 yrs old (P less than 0.05). Age-related differences in CL or Vss were also observed when these parameters were normalized by body surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of converting from intravenous to oral administration of cyclosporin A in pediatric allogeneic hematopoietic stem cell transplant recipients

“…The total clearance of CsA tended to be greater in the pediatric transplant population when compared to the adult transplant groups 16,17,19 and patients 0 to 10 years old had a significantly higher CsA CL than those 411 years old. 16 In this study, mean clearance (CL)7s.d.…”

“…16 In this study, mean clearance (CL)7s.d. was 480.97103.7, 414.97137.1 and 320751.8 ml/h/kg in patients with o20 kg , 20-40 kg and 440 kg of body weight, respectively.…”

“…12 In general, many drugs administered to children are characterized by a substantially faster elimination than in adults; however, there are limited data on the pharmacokinetics of CsA in pediatric transplant recipients. 16,17 Some studies have evaluated the pharmacokinetic properties of CsA in children undergoing organ transplantation. [18][19][20][21][22][23][24][25][26][27] However, few published data are available for the pediatric HSCT population.…”

Effect of cyclophosphamide on serum cyclosporine levels at the conditioning of hematopoietic stem cell transplantation

“…5,6,38 Physical attributes, such as gender and age, have also been reported related to the serum CsA concentrations. 39,40 As younger people have a more rapid CL and a larger Vss than the elderly, caution with serum CsA doses based on differences in age has been claimed to be required. 39 Our results showed that the serum CsA concentration was not influenced by age, gender, administration of fluconazole, or administration of antibacterials.…”

“…39,40 As younger people have a more rapid CL and a larger Vss than the elderly, caution with serum CsA doses based on differences in age has been claimed to be required. 39 Our results showed that the serum CsA concentration was not influenced by age, gender, administration of fluconazole, or administration of antibacterials. Several studies have indicated that transplantations from unrelated donors are associated with higher risks of both acute GVHD and regimen-related toxicity.…”