Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis

Objectives: To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. Methods: We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC(0-8)) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). Results: All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC(0-8) indinavir decreased by 4.4% (90% CI, -27.5% to -26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, -37.3% to +9%, P=0.25) in phase III. Control group mean AUC(0-8) decreased by 21.5% (90% CI, -43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle-oindinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle-indinavir trials revealed a non-significant pooled mean difference of 1% in AUC(0-8) (95% CI, -53% to 55%, P=0.97). Conclusions: Indinavir levels were not reduced significantly in the presence of milk thistle.

The effect of salinity on plant available water

Salinity acts to inhibit plant access to soil water by increasing the osmotic strength of the soil solution. As the soil dries, the soil solution becomes increasingly concentrated, further limiting plant access to soil water. An experiment was conducted to examine the effect of salt on plant available water in a heavy clay soil, using a relatively salt tolerant species, wheat ‘Kennedy’, and a more salt sensitive species, chickpea ‘Jimbour’. Sodium chloride was applied to Red Ferrosol at 10 rates from 0 to 3 g/kg. Plants were initially maintained at field capacity. After 3 weeks, plants had become established and watering was ceased. The plants then grew using the water stored in the soil. Once permanent wilting point was reached plants were harvested, and soil water content was measured. The results showed that without salt stress, wheat and chickpea extracted approximately the same amount of water. However, as the salt concentration increased, the ability of chickpea to extract water was severely impaired, while wheat’s ability to extract water was not affected over the range of concentrations examined. Growth of both wheat and chickpea was reduced even from low salt concentrations. Possible explanations for this are that the effect on growth is due to Cl- toxicity and that this occurs at lower concentrations than the osmotic effect of salinity, or that the metabolic demands of maintaining plant water balance and extracting soil water under saline conditions result in reduced growth.