Serum theophylline after multiple dosing with transdermal gels in cats

Abstract

Objectives Our objectives were, first, to determine if therapeutic serum theophylline concentrations could be achieved using long-term, once-daily dosing of transdermal theophylline and, secondarily, to evaluate the difference between two transdermal theophylline formulations. Methods Seven healthy cats, 1–10 years of age, were evaluated in a two-way, randomized, double-blinded, crossover study. Participants received transdermal theophylline at 15 mg/kg for 21 days in either pluronic lecithin organogel (PLO) or Lipoderm formulation. On day 22, blood was collected 2, 6, 14 and 24 h after dosing. After a 14 day washout period, blood was collected to verify non-detectible theophylline concentrations. The alternate formulation was administered for 21 days, and sampling was repeated. Serum theophylline concentrations were determined using an automated immunoassay. Serum concentrations were compared between formulations using a two-way random-measures ANOVA and over time within a formulation using a repeated-measures ANOVA. Results Therapeutic serum theophylline concentrations were achieved for 2/7 cats in each group. Of 56 serum theophylline measurements obtained, only seven (13%) were within the therapeutic range. No significant difference was detected in drug concentrations achieved by the transdermal formulations at any time point. In addition, no significant difference in serum theophylline concentrations was noted between time points for PLO ( P = 0.751) or Lipoderm ( P = 0.107). Conclusions and relevance Once-daily transdermal dosing of theophylline does not reliably achieve therapeutic concentrations. Individual cats may achieve therapeutic concentrations. No significant difference was noted between PLO and Lipoderm formulations. Therefore, transdermal theophylline formulations should not be considered as a first-line therapy in feline asthma patients.