Pharmacokinetics of theophylline in preterm neonates during the first month of life

The present work aimed to estimate the theophylline pharmacokinetic parameters [TH-PKP] in preterm neonates with apnea during the first month of life in order to optimize its dosage regimen. Fifty preterm neonates enrolled in the study with recurrent apnea were admitted during 1998-2000 to the Neonatal Intensive Care Unit of Maternity and Children's Hospital, Al-Mosaida, Jeddah, Kingdom of Saudi Arabia. Criteria for this study were preterm with gestational age [GA] of 26-33 weeks [mean +/- SD 30 +/- 3.9]. They received TH of 3-6 mg/kg loading dose [LD] followed by maintenance dose [MD] of 0.5 - 3.0 mg/kg/12 hours. Eight of these patients received phenobarbital and 19 received cimetidine concomitantly for at least 7 days. Blood samples were taken one hour post LD and at steady state [Css]. Theophylline levels were determined by fluorescence polarization immunoassay. Phenobarbital significantly enhanced TH clearance [CL] and reduced its half-life [t0.5] but cimetidine had no significant effect. Excluding patients receiving phenobarbital. The mean +/- SD TH-PKP were volume of distribution [Vd] = 0.77 +/- 0.25 L/kg; elimination rate constant [Ke] = 0.027 +/- 0.011 h-1; CL = 0.019 +/- 0.006 L/h/kg, t0.5 = 30.7 +/- 12.1. There was marked intra patient variability in all TH-PKP. In view of the results and practical considerations, initial dosage regimen to attain a TH Css level within the therapeutic range [6-12 ug/ml] was suggested: LD 6-7 mg/kg, MD 1.5 - 2.0 mg/kg/12 hours. To compensate for maturation changes or drug interaction, a method, based on estimation of individual TH CL, was described for adjusting MD

evaluation of theophylline dosing. suggested by the Saudi national protocol for children with severe asthma

To evaluate the impact of Saudi national protocol on the diagnosis and management of asthma for optimizing theophylline use in children with severe asthma. To also review theophylline clearance and provide guidelines for individualization of doses. Theophylline level was estimated in blood samples of 66 children with severe asthma who were admitted to King Abdulaziz University Hospital during the period 1998-1999. The theophylline doses given to these patients was reviewed and patients were categorized into 2 groups: Group one had received doses recommended by Saudi national protocol +/- 10%, group 2 had received doses <90% of that recommended by Saudi national protocol. The distribution of theophylline levels in blood samples of each group was estimated. Theophylline steady state level was used to estimate theophylline clearance using a standard pharmacokinetic equation. Out of the total samples from group one, 70% of theophylline levels were within therapeutic range, while only 10% of the total samples of group 2 were within therapeutic range. The mean theophylline clearance in children [1-8 years] was estimated as 0.092 +/- 0.023 and was found significantly higher than the mean theophylline clearance [0.069 +/- 0.014] which is observed in older children [9-13 years]. Saudi national protocol theophylline dose guidelines had a favorable impact on the optimization of theophylline use in children with severe asthma. Guidelines that ensure accurate adjustment of doses on individual basis in view of drug level were suggested

Effect of renal transplantation on hematological profile of patients with end-stage renal disease

Abnormalities in haematological values in end-stage renal disease [ESRD] patients and their correction after successful kidney transplantation were investigated. A group of 41 patients were studied before and up to 1 year after transplantation. Values were compared with those obtained in 34 matched healthy volunteers. ESRD patients had significantly lower mean haemoglobin [Hb], haematocrit [Hct], and red blood cells [RBC] values [7.6 +/- 1.3 g/dl; 0.25 +/- 0.13I/I and 2.8 +/- 0.5x 10 12/I respectively] than healthy volunteers [14.1 +/- 1.9g/dl, 0.45 +/- 0.06 I/I and 5.1 +/- 0.7 x 10 12/I, respectively]. They also had slightly lower mean platelet, lymphocyte and monocyte counts. All other haematological parameters measured were normal. Correction of anaemia after renal transplantation began promptly, but progressed slowly. Only 21.9% of all patients achieved a normal range of Hb by the end of 3 months and 53.7% at the end of 1 year. Early graft rejection adversely affected early recovery of Hb values. At all time points post-transplant, mean Hb values were significantly higher [p<0.05-p<0.001] in recipients of kidneys from living related donors than in recipients of cadaveric kidneys [e.g. 13.3 +/- 1.0 g/dl vs 9.8 +/- 0.7 g/dl after 6 months]. Female patients tended to recover their normal Hb values faster than males. No role for the immunosuppressor cyclosporin-A in the rate of resolution of anaemia was found. The results show that anaemia associated with chronic renal failure persists in about half of all patients 1 year after successful kidney transplantation. Its resolution is better in recipients of kidneys from living donors, but hampered by graft rejection