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Simple Summary: The purpose of this study was to investigate the bioavailability and metabolic path of thymol, a major constituent of Thymus vulgaris L., in the rabbit organism. Oral bioavailability is a key parameter affecting the efficacy of substances, but it is not surprising that it does not correlate satisfactorily with efficacy. The main limitation factors are rate of absorption, metabolism, and excretion processes. In this work, the thymol metabolic path in the rabbit organism was determined for the first time after its sustained oral administration. We confirm intensive absorption of thymol from the gastrointestinal tract; our results point to metabolism and accumulation in kidney tissue and intensive metabolic and excretion processes in the liver. Some metabolic processes were present also after thymol withdrawal. Thymol as a lipophilic substance was found only in trace amounts in fat and muscle tissue as a consequence of its conversion into hydrophilic metabolite and greater elimination in the rabbit organism. This paper highlights the insufficient knowledge of modes of action of plant compounds in animal organisms. The objective of this study was the detection of thymol in rabbit plasma, tissues, large intestinal content, and faeces. Forty-eight rabbits were divided into control and experimental groups (thymol 250 mg/kg feed). Thymol was administered for 21 days and then withdrawn for 7 days. Concentration of thymol in the intestinal wall (IW) was significantly higher than in plasma (p < 0.05) and liver (p < 0.05); in the kidneys it was significantly higher than in plasma (p < 0.05) and liver (p < 0.05) during thymol addition. Thymol in IW was significantly higher than in plasma also after withdrawal (p < 0.01). Significant correlation (rs = −1.000, p < 0.01) between IW and plasma points to the intensive absorption of thymol from the intestine, while the correlation between plasma and liver (rs = 0.786, p < 0.05) indicates intensive biotransformation and excretion processes in liver. Significant correlation between liver and kidney (rs = 0.738, p < 0.05) confirms the intensive metabolism of thymol in the kidney. During the withdrawal period, thymol was detected above trace amounts only in faeces, and was significantly higher than in the colon during both periods (p < 0.01). Results show intensive biotransformation of thymol in the rabbit organism. [ABSTRACT FROM AUTHOR]

Simple Summary: So far, the study of the bioactivity of thymol, a major constituent of Thymus vulgaris L., in the animal organism has received little attention. Our study could give us answers to questions about whether thymol accumulates in the rabbit organism after its sustained administration and if it is also able to exhibit its beneficial properties for a longer period. Thymol in powder form at the concentration 250-mg/kg feed was added to the rabbit diet for 21 days and withdrawn for the next seven days. We confirmed that thymol was sufficiently absorbed from the gastrointestinal tract and was able to express its biological activity not only during application but, also, after withdrawal. Further studies are needed to clarify the biotransformation and bioavailability of thymol in the rabbit organism with respect to the specific features of rabbit digestion. Thymol concentrations in rabbit plasma, intestinal wall (IW) and faeces were detected, and the effects of thymol application and withdrawal on biochemical, antioxidant parameters and fatty acids (FA) in blood (B) and muscle (M) were studied. Forty-eight rabbits were divided into two experimental groups (control, C and with thymol 250-mg/kg feed, T). Thymol was administered for 21 days (TA) and withdrawn for seven days (TW). Thymol in plasma correlated with that in the IW (Spearman′s correlation coefficient (rs) = −1.000, p = 0.0167, TA) and was detected in faeces (TA and TW). In TA alkaline phosphatase (p = 0.0183), cholesterol (p = 0.0228), malondialdehyde (p = 0.003), glutathione peroxidase (p = 0.0177) in B and lactate dehydrogenase (M, p = 0.0411) decreased; monounsaturated FA (p = 0.0104) and α-linolenic acid (p = 0.0227) in M increased. In TW urea (p = 0.0079), docosapentaenoic acid (p = 0.0069) in M increased; linoleic acid (p = 0.0070), ∑ n−6 (p = 0.0007) in M and triglycerides decreased (B, p = 0.0317). In TA and TW, the total protein (p = 0.0025 and 0.0079), creatinine (B; p = 0.0357 and 0.0159) and oleic acid (M; p = 0.0104 and 0.0006) increased. Thymol was efficiently absorbed from the intestine and demonstrated its biological activity in blood and the muscles. [ABSTRACT FROM AUTHOR]