Terbinafine In Plasma Research Articles

Pharmacokinetics of Nebulized Terbinafine in Plasma and Keratin of Northwestern Pond Turtles (Actinemys marmorata) Associated with Emydomycosis

The Northwestern pond turtle ( Actinemys marmorata ) is native to Washington State, USA and has developed a grossly evident form of shell disease affecting a large percentage of the free-ranging population in this state. Emydomyces testavorans is a novel fungus in the order Onygenales that is the presumed causative agent for shell disease in the Northwestern pond turtle. Terbinafine hydrochloride is a lipophilic allylamine broad spectrum antifungal that penetrates keratin and concentrates in the stratum corneum. This study evaluated the drug concentration in the plasma and keratin of 18 Northwestern pond turtles after nebulization with 18 mg terbinafine solution (2 mg/ml) once a day for 28 days. Blood and keratin samples were collected serially during the course of treatment, and for 14 days following the last dose. Plasma and keratin were analyzed by high-performance liquid chromatography. No significant concentrations of terbinafine were found in the plasma of the turtles. Terbinafine in turtle keratin peaked after 16 days of treatment and maintained therapeutic concentrations for 14 days post treatment. Turtle shell lesions also showed signs of clinical improvement post-therapy. Nebulization of terbinafine is recommended for the treatment of shell disease secondary to Emydomyces testavorans , however pulse antifungal therapy is likely needed to prevent disease from reoccurring.

Quantitative analysis of terbinafine (Lamisil) in human and minipig plasma by liquid chromatography tandem mass spectrometry.

A method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of terbinafine in human and minipig plasma has been developed and validated. The method used positive-ion mode for monitoring terbinafine, and used a stable isotope labelled terbinafine as the internal standard. Subsequent to acetonitrile protein precipitation, the supernatant was directly (unfiltered) injected onto the LC column (retention time approximately 4.3 min) for analysis. Interday and intraday accuracy and precision were assessed from the relative recoveries (observed concentration in percent of the nominal value) of spiked samples analyzed on three different days. The lower limit of quantitation (LLOQ) was 0.0679 ng/mL in human and minipig using a plasma sample volume of 0.08 mL. The method was fast, specific, and exhibited ruggedness. Furthermore, the use of turbulent flow chromatography (TurboFlow LC/MS/MS) coupled to mass spectrometry for direct analysis of terbinafine in plasma is discussed. The technique allowed direct introduction of plasma with satisfactory chromatographic peak shape and increased throughput.

Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once daily for 7 and 14 days.

In earlier skin pharmacokinetic studies we have shown that terbinafine is rapidly delivered to the stratum corneum, nails and hair both through sebum and by direct diffusion through dermis-epidermis. In the present study the skin pharmacokinetic profile of terbinafine was studied in two groups of eight human male volunteers during and after 250 mg orally once daily for 7 and 14 days. In the 7-day study high terbinafine levels were found in sebum (19.0 micrograms/g) and stratum corneum (2.5 micrograms/g), and a concentration in stratum corneum above the minimal inhibitory concentration for most dermatophytes was still found 48 days after the last day of medication. Terbinafine was found in peripheral nail clippings after 7 days of medication and the concentration was, in the 7-day study, 0.5 microgram/g 1 day after stopping medication; it was still 0.2 microgram/g 90 days after stopping treatment. The results in the 14-day study were in parallel with, but higher than, in the 7-day study. The elimination of terbinafine from several compartments is biphasic, with a faster initial elimination followed by a slower secondary elimination. For nails, the elimination is slower compared with the other compartments. The results indicate that terbinafine may be effective in short-term treatment of several dermatophytoses. The concentration of 0.2 microgram/g of terbinafine found in nails 90 days after stopping medication, following 7 days of treatment, indicates that the duration of therapy, even in tinea ungium, may be shorter than is currently the case.

Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once per day for four weeks.

The distribution of terbinafine in stratum corneum dermis-epidermis (without stratum corneum), sebum, hair, nails and plasma was studied in human male volunteers during and after 250 mg orally once daily for 28 days. The highest concentration was seen in sebum, 56.07 micrograms/g, after 14 days of therapy. The concentration was still 1.0 microgram/g 44 days after stop of medication. In stratum corneum the highest concentration, 14.4 micrograms/g, was seen 1 day after the last day of therapy, and it was 2.1 micrograms/g 44 days after stop of medication. The concentrations in hair and nails were lower with a maximum of 2.36 and 0.39 micrograms/g respectively, 1 day after stop of therapy, and still 0.21 microgram/g in hair and 0.09 microgram/g in nails 55 days after the last day of medication. With the exception of nails, all other tissue levels were at all times above the plasma concentrations. For nails, tissue levels exceeded that of plasma as early as 1 day after stop of medication, and this difference continued to increase until the last day of tissue sampling, 55 days after the last tablet. These results indicate that terbinafine is delivered to the stratum corneum through sebum and to a minor extent by direct diffusion through dermis-epidermis. Probably short-term therapy with terbinafine may be effective in the treatment of several dermatomycoses, due to the strong binding of terbinafine to stratum corneum for a long time after stop of medication.(ABSTRACT TRUNCATED AT 250 WORDS)