Population pharmacokinetics of Carbamazepine and optimising its use in Saudi epileptic children

Abstract

The objective of this study is the identification of Carbamazepine (CBZ) phamacokinetic parameters (PKP) and to suggest CBZ optimal therapeutic range (OTR) to Saudi epileptic children (SEC). 493 SEC with means age 8.23 ± 3.907 years, body weight 26.18 ± 12.10 kg, were all treated with CBZ, therapeutic drug monitoring (TDM) at Drug Monitoring Unit (DMU). In the retrospective (RS), 603 samples of 186 males and 155 females were from medical records at King Abdulaziz University Hospital (KAUH). Patients, diagnoses, clinical and laboratory investigations were taken from Maternity & Children Hospital. In the prospective (PS), 255 samples from 92 males and 48 females were placed on CBZ maintenance dose (MD) of 442.859 ± 184.44 mg/day. In the pharmacokinetics (PK-S), 6 males and 6 females had no CBZ before. Given a single loading dose (LD) with mean 4.19 ± 1.64 mg/kg, 4 to 8 samples were collected for calculation of PKP. For OTR determination, CBZ MD sampling continued up to 4 months. The following results were obtained: (a) Pharmacokinetic Parameters - Cl [(L/h)/kg] = 0.3526 ± 0.233; Ke (h-1) = 0.0837 ± 0.056; Cmax (mg/ml) = 2.52 ± 1.447; T_1/2 (h) = 11.68 ± 6.88; Tmax (h) = 4.38 ± 1.992; Vd (L/kg) = 6.47 ± 6.022; AUC [(µg/ml)/h] = 13.49 ± 6.0904. (b) Samples distribution (%) for RS and PS: 73.63, 92.5 therapeutic range, 22.22, 6.27 sub therapeutic, 4.15, 1.23 toxic, respectively. (c) One week after treatment, 83.3% were seizure free, a patient continued after the 1st month. Correlation was stronger between seizures numbers VS blood levels mg/ml (r = -0.97) than VS dose mg/kg BW (r = -0.92). (d) Toxicity: 2- Steven Johnson Syndrome, 1- osteoporosis and 1- dynamic/kinetic interaction. In conclusion, actual CBZ PKP values in SEC were defined. No direct correlation between ethnicity and blood levels. Similarity to findings conducted on non-Saudi healthy or adult volunteer confirms the importance of continuing this work using modern technology to differentiate between the genuine CBZ PKP values and influences by interfering modifiers.

Keywords: Epilepsy, pharmacokinetic, Carbamazepine.