Pharmacokinetic analysis of thymol, carvacrol and diallyl disulfide after intramammary and topical applications in healthy organic dairy cattle

Abstract

Mastitis is among the most costly concerns for dairy producers whether cattle are managed conventionally or organically. Unfortunately, there are no USFDA-approved mastitis treatments that allow dairy cows in the United States to maintain organic dairy status. We investigated the plasma pharmacokinetics of three organic mastitis products currently used by organic producers and organic dairy veterinarians. Those products include intramammary, topical and intravaginal preparations, each dosed at two levels. Additionally, tissue data were collected for kidney, liver and fat in order to estimate a withholding time for each of the products. The lower limit of quantification (LOQ) and lower limit of detection (LOD) were 0.001 and 0.0005 µg ml, respectively, in plasma and all tissues except fat for both thymol and carvacrol. Fat had an LOQ of 0.01 µg ml and an LOD of 0.005 µg ml for thymol and carvacrol. Diallyl disulfide had an LOQ of 0.005 µg ml and LOD of 0.001 µg ml in all tissues. For diallyl disulfide (garlic), no levels above 0.001 µg ml were measurable in plasma or tissues. For topical and intramammary products, levels were measurable in the plasma, liver, kidney and fat up to 72 h after the last dose. The plasma half-lives were short for thymol (approximately 1.6 h) and carvacrol (approximately 1.5 h), whereas the estimated half-lives for these substances in tissues ranged from 13.9 to 31.5 h for thymol and from 16.9 to 25 h for carvacrol. The predicted amount of time that the molecules would be found in the body based on the slowest depletion time of liver tissue was 13 days for thymol and 10 days for carvacrol. The apparent half-life of topically applied carvacrol was approximately 4.5 h in plasma, with an estimated withhold time of 10 days. These times were calculated using the USFDA's tolerance limit method for meat withdrawal times.

High Activity of Selective Essential Oils against Stationary PhaseBorrelia burgdorferi

“…Identification of active components or active component combinations from essential oils may help to eliminate the quality difference of natural products. However, we were able to identify carvacrol as the most active ingredient in oregano essential oil, and its pharmacokinetics has been studied as a feed addition in pigs (25) and topical oil in cattle (26). In the rat model, the calculated LD50 of carvacrol is 471.2 mg/kg (27).…”

Efficacy of a terpinen-4-ol based dipping for post-milking teat disinfection in the prevention of mastitis in dairy sheep

“…Several studies were performed to evaluate the effectiveness of essential oils in dairy animals, particularly in cows (39)(40)(41); however, no studies have been carried out on the preventative efficacy of the T-4-ol against bacterial mastitis in dairy ewes. T-4-ol was the active principle of a post-dipping formula developed by Istituto Superiore di Sanità (Patent application n°0 8425431.7) for the prevention of mastitis in dairy animals.…”

Effect of Carvacrol Tested on Different in vivo and in vitro Experimental Studies: Systematic Review

“…The predicted amount of time of the molecules found in the body based on the slower depletion time in liver tissue was 10 days for carvacrol. [18] 30, 50 and 70 mg/kg b.w. Bone marrow cells from rats.…”

“…[17] PARP: Poly-(ADPribose)-Polymerase. understanding the half-life and the half-life in the carvacrol [18] is elementary to use effectively in the clinic, as well as the moment of intervention with this phytotherapic, since the same in certain dosages can decrease the cellular division [19], being thus a strong combatant of cells carcinogenic in the early stages.…”