Letter to the Editor Nephron 1999;81:366–367 Effect of Seasonal Changes on the Cyclosporine A Blood Levels in Renal Transplant Recipients during Childhood Salih Kavukçu a Alper Soylu a Mehmet Türkmen a Seymen Bora b Hülya Güven c Hüseyin Gülay b Departments of a Pediatrics, b General Surgery and c Pharmacology, Dokuz Eylül University Medical Faculty, I ˙ zmir, Turkey Dr. Salih Kavukçu Department of Pediatrics Dokuz Eylül University Medical Faculty TR–35280 I ˙ zmir (Turkey) Tel./Fax +90 232 231 2610 ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 1999 S. Karger AG, Basel 0028–2766/99/0813–0366$17.50/0 Accessible online at: http://BioMedNet.com/karger Dear Sir, The food consumption of children is re- lated to seasonal changes in developing countries. Some natural substances like fla- vonoids, found in various fruits and vegeta- bles, have been reported to inhibit the cyto- chrome P-450 oxidase system which is re- sponsible for the major part of the metabo- lism of cyclosporine A (CsA) [1, 2]. The blood CsA level has been reported to be high- er when the drug was administered with juices of flavonoid-containing fruits, espe- cially grapefruit [3]. Our region, located on the east shore of the Aegean Sea, has the characteristic Mediterranean climate and many fruits and vegetables, like grapefruit, leek and lettuce, rich in flavonoids, are culti- vatable in this region, especially in the win- ter months. We wanted to evaluate retrospectively the relationship of seasonal changes to CsA blood levels in children with renal trans- plants living in a Mediterranean climate. Starting 3 months after renal transplant, 7 children (6 males, mean age 13.5 B 1.1 years; mean posttransplantation follow-up 35.3 B 3.9 months) were evaluated retro- spectively to study their monthly blood CsA levels. All of the patients were treated with similar doses of CsA (5 mg/kg/day), azathio- prine (1 mg/kg/day) and prednisolone (10 mg/day) after this period. In addition, pa- rameters related to the fluid and electrolyte balance, like serum creatinine and electro- lytes, were evaluated to exclude the effect of alterations in these parameters on the blood level of the drug. Then, winter (December to February) and summer (June to August) val- ues were compared. Serum creatinine and electrolytes were normal in all of the patients and did not dif- fer seasonally. Blood CsA levels were higher during the summer in 6 of 7 patients (85.7%) and the cumulative CsA values were signifi- cantly higher during the summer in compari- son to the winter (123.7 B 6.8 and 108.6 B 8.2 ng/ml, respectively, p ! 0.02). During the winter the mean blood CsA levels were less than the therapeutic range (100–150 ng/ml) in 2 of 7 patients (28.5%), while all of the patients had levels within therapeutic range during the summer, except for 1 patient who had even higher values (table 1). CsA may cause arteriolar changes, inter- stitial fibrosis and progressive renal failure [4] and thus, its blood level should be kept within the therapeutic range (100–150 ng/ml 3 months after transplantation). CsA is me- tabolized by the cytochrome P-450 mixed function oxidase system which is effected by various drugs and substances like steroids Table 1. Mean whole-blood cyclosporine A (CsA, normal therapeut- ic range 100–150 ng/ml) levels determined during the winter and summer months and comparison of these values in each patient (mean B SE) Patient No. CsA level, ng/ml summer winter p 1 118.1B7.5 96.1B15.7 1 0.05 2 105.0B17.5 121.0B7.7 1 0.05 3 118.2B21.4 114.1B20.3 1 0.05 4 102.8B18.7 64.6B9.6 1 0.05 5 146.5B18.2 125.2B28.7 1 0.05 6 171.0B22.7 130.0B21.3 1 0.05 7 148.6B24.5 133.1B29.3 1 0.05 Cumulative 123.7B6.8 108.6B8.2 ! 0.05 Downloaded by: MacQuarie University 137.111.162.20 - 2/24/2019 8:41:12 AM