Pharmacokinetics And Absolute Bioavailability Of Terbinafine Hydrochloride Tablets In Dogs

Terbinafine hydrochloride is the second generation of allylamine antifungal agent which has a broad spectrum activity.Because of its antifungal mechanism clearly,antifungal spectrum widely,dosage form numerously,applicability widely and efficacy.Terbinafine hydrochloride has been already widely used in human clinical medicine,but its research on animals is relatively less.In order to obtain pharmacokinetic parameters,dogs were injected terbinafine hydrochloride solution or administered orally with terbinafine hydrochloride tablets.The pharmacokinetic process and absolute bioavailability of terbinafine in dogs were used to provide a theoretical basis for developing a reasonable dosage regimen and reducing adverse reaction effectively.In this experiment,eight healthy beagle dogs(four male dogs and four female dogs)were randomly divided into two groups,group A and group B.In the first phase,a single dose of 2%terbinafine hydrochloride solution(5 mg/kg bw)was administrated to group A via intravenous injection,while the terbinafine hydrochloride tablets at the dose of 20 mg/kg bw was administrated to group B via oral.In the second phase,group A and group B exchange their first stage of administration.In addition to set up a parallel group C,which has eight healthy beagle dogs(four male dogs and four female dogs).A single dose of terbinafine hydrochloride tablets(10 mg/kg bw)was administrated to group C via oral.Blood samples were collected at predetermined time point after administration.And the Terbinafine concentration in plasma was tested by high performance liquid chromatography tandem DAD detector(HPLC-DAD),with a mobilephase of methanol-0.1%phosphoric acid aqueous solution(59:41,V/V).Detection using external standard method.And the concentration-time data of terbinafine in plasma were analyzed with Winnonlin5.2 software to obtain pharmacokinetic parameters.The main pharmacokinetic parameters after a single dose of 5 mg/kg bw intravenous injection of terbinafine hydrochloride solution were as follows:the mean elimination half-life(T1/2)was 16.16 h,the mean residence time(MRT)was 2.44 h,the mean area under the curve from 0?24 h(AUC0?24 h)was 1.80 h·?g/mL,the mean apparent volume of distribution(Vd)was 48.78 L/kg,the mean plasma clearance(CL)was 2.42 L/(kg·h).The main pharmacokinetic parameters after a single dose of 10 mg/kg bw and 20 mg/kg bw oral of terbinafine hydrochloride tablets were as follows:the mean elimination half-life(T1/2)was 19.25 and 18.15 h,the mean peak time(Tmax)was 1.69 and 1.88 h,the mean peak concentration(Cmax)was 0.16 and 0.32 ?g/mL,the mean residence time(MRT)was 5.22 and 5.02 h,the mean area under the curve from 0?24 h(AUC0?24h)was 0.62 and 1.09 h·?g/mL,the mean absolute bioavailability from 0?24 h(F0?24 h)was 17.08%and 16.59%.The results showed that terbinafine was widely distributed in dogs,and the elimination was slow.Terbinafine absorbed quickly and incompletely in dogs after oral administration of terbinafine hydrochloride tablets.At the single dose of 10 mg/kg bw and 20 mg/kg bw oral of terbinafine hydrochloride tablets,there were no significant differences in the Tmax,T1/2,MRT or F0?24h,but the Tmax and AUC0?24h were proportional to the dose-dependent increase.