Effect of Time of Sample Collection, Initial Dose, Weight and Duration of Therapy on Serum Phenobarbital Levels in Dogs with Epilepsy
Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow
Phenobarbital (Pb) is the most commonly drug used in the management of epilepsy. Pb is primarily metabolised in the liver via the hepatic microsomal enzyme system. Longer term Pb therapy results in induction of the hepatic microsomal enzyme system, increasing the rate of metabolism and resulting in higher doses of oral Pb in order to maintain the same serum Pb level. Moreover, body mass is inversely proportional to the metabolic rate which then influences the turnover rate at the cellular level and thus the dose required in different individuals.
The aim of this study was to assess the relationship between initial label recommended doses of Pb and the proportion of dogs reaching therapeutic serum level; the relationship between weight and dose required to reach therapeutic serum level, the significance of timing of blood collection in relation to serum Pb level in dogs on different doses; and to investigate the effects of duration of treatment on the serum Pb level relative to the dose administered.
Data was collected retrospectively from the Vétoquinol UK Pb monitoring voucher scheme (n=2021). Recorded data included signalment, weight, total daily dose, time of sampling (trough or non-trough), length of treatment and serum Pb level. For statistical purposes the trough and non-trough groups were divided into a total daily dose of 2-5mg/Kg, >5-8mg/Kg and >8mg/Kg; the length of treatment was grouped as <2 weeks (w), 2-<4w, 4-<12w, 12w-< 1year and >1 year; and the weight analysis included all dogs divided as <10Kg, 10-30kg and > 30Kg.within the therapeutic range that had serum Pb level checked between 2-4w after initiation of therapy.
The results revealed that from dogs started on Pb therapy at the manufacturer's recommended dose (2-5mg/kg/day), 90 out of 220 reached therapeutic serum level at first monitoring, but if started at 5-8mg/kg /day, 40 out of 50 reached therapeutic levels (P < 0.001); of the 247 dogs evaluated for starting dose in relation to weight a highly significant inverse relation was found between weight and dose/ Kg/day (P<0.001);at a total daily dose of Pb of <8mg/kg the ratio of serum level to total daily dose for the trough group (n=799) was only 2.7% lower than that of the non-trough group (n=464, P = 0.3029), but at >8mg/kg the trough group (n=166) was significantly lower (17.8%, p=0.01114) than the non-trough group (n=86); and therapy duration of <2w the ratio was 18.31 (n=106), at 2-4w 16.94 (n=214, P=0.17), at 4-12w 16.46 (n=310, P=0.05), at 12w to 1-year 15.96 (n=315, P=0.01), and at >1-year 16.29 (n=609, P=0.02).
In conclusion, higher initial doses are required to reach therapeutic level and choice of initial dose should take into consideration body weight. In dogs on higher daily doses of Pb, consistency of timing of blood sampling is important to ensure accurate comparison between serum Pb levels. Animals on a long term therapy will need adjustment of dose throughout treatment.