Pharmacokinetics in Plants: Carbamazepine and Its Interactions with Lamotrigine

Abstract

Carbamazepine and lamotrigine prescribed antiepileptic drugs are highly persistent in the environment and were detected in crops irrigated with reclaimed wastewater. This study reports pharmacokinetics of the two drugs and their metabolites in cucumber plants under hydroponic culture, testing their uptake, translocation, and transformation over 96 h in single and bisolute systems at varying pH. Ruling out root adsorption and transformations in the nutrient solution, we demonstrate that carbamazepine root uptake is largely affected by the concentration gradient across the membrane. Unlike carbamazepine, lamotrigine is adsorbed to the root and undergoes ion trapping in root cells thus its translocation to the shoots is limited. On the basis of that, carbamazepine uptake was not affected by the presence of lamotrigine, while lamotrigine uptake was enhanced in the presence of carbamazepine. Transformation of carbamazepine in the roots was slightly reduced in the presence of lamotrigine. Carbamazepine metabolism was far more pronounced in the shoots than in the roots, indicating that most of the metabolism occurs in the leaves, probably due to higher concentration and longer residence time. This study indicates that the uptake of small nonionic pharmaceuticals is passive and governed by diffusion across the root membrane.

Screening of Emerging Pollutants (EPs) in Estuarine Water and Phytoremediation Capacity of Tripolium pannonicum under Controlled Conditions

“…However, previous studies have been able to demonstrate the degradation of CBZ. For example, some CBZ metabolites such as EP-CBZ, DiOH-CBZ, 2-OH-CBZ and 3-OH-CBZ have been detected in cucumber plants [42]. In this latter experiment, the incubation time as well as the xenobiotic concentrations were lower compared to our experiment, yet a degradation of the substance could be determined.…”

“…Besides, the experiment identified a total of 21 transformation products [41]. In other previous experiment carried out by Goldstein et al [42], in which cucumber plants were exposed under hydroponic conditions to a CBZ concentration of 0.43 mg L −1 , a CBZ degradation of more than 10% could be detected in the first 96 h. The experiment also showed that different drugs can influence each other in their uptake rate and metabolism.…”

Insight into the distribution of pharmaceuticals in soil-water-plant systems

“…The less translocation of lamotrigine relative to carbamazepine was also observed in sweet potato, carrot, tomato, and cucumber (Goldstein et al, 2014;Malchi et al, 2014). Goldstein et al (2018) demonstrated that the transpiration stream concentration factor of carbamazepine (~0.7-0.9) in cucumber was about 4.6 times higher than that of lamotrigine (~0.1-0.25), which is similar to the TF difference (~4 times) in radish between the two chemicals. The TF values of intermediate hydrophobic compounds monensin (log Dow = 1.65) and tylosin (log Dow = 1.47) was 0 and 0.4, respectively, which are much less than the predicted transport based on the hydrophobicity (Tanoue et al, 2012).…”

Reclaimed water driven lettuce cultivation in a hydroponic system: the need of micropollutant removal by advanced wastewater treatment

“…Plant uptake and translocation within plants are attributed to physico-chemical properties of the micropollutants, particularly to lipophilicity and charge (Goldstein et al 2014;Yahyazadeh et al 2017). The less polar carbamazepine (LH 2 O: 0.15 g L −1 ; log K ow : 2.45; pK A : 13.9) (all data from PubChem, accessed on 03/30/2021) is taken up by the lettuce root hairs and is passed through root epidermis, cortex, and endodermis with Casparian strip due to its nonionic character in a wide pH range (Goldstein et al 2018). Thus, it can easily cross selectively permeable plasma membranes and is subsequently translocated through the xylem into the lettuce shoots (Herklotz et al 2010;Li et al 2018).…”