Pharmacokinetics of the Recalcitrant Drug Lamotrigine: Identification and Distribution of Metabolites in Cucumber Plants.

Treated wastewater is an important source of water for irrigation. As a result, irrigated crops are chronically exposed to wastewater-derived pharmaceuticals, such as the anticonvulsant drug lamotrigine. Lamotrigine is known to be taken up by plants, but its plant-derived metabolites and their distribution in different plant organs are unknown. This study aimed to detect and identify metabolites of lamotrigine in cucumber plants grown for 35 days in a hydroponic solution by using LC-MS/MS (Orbitrap) analysis. Our data showed that 96% of the lamotrigine taken up was metabolized. Sixteen metabolites possessing a lamotrigine core structure were detected. Reference standards confirmed two; five were tentatively identified, and nine molecular formulas were assigned. The data suggest that lamotrigine is metabolized via N-carbamylation, N-glucosidation, N-alkylation, N-formylation, N-oxidation, and amidine hydrolysis. The metabolites LTG-N2-oxide, M284, M312, and M370 were most likely produced in the roots and were translocated to the leaves. Metabolites M272, M312, M314, M354, M368, M370, and M418 were dominant in leaves. Only a few metabolites were detected in the fruits. With an increasing exposure time, lamotrigine leaf concentrations decreased because of continuous metabolism. Our data showed that the metabolism of lamotrigine in a plant is fast and that a majority of metabolites are concentrated in the roots and leaves.

Chronic ocular complications in lamotrigine vs. trimethoprim-sulfamethoxazole induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

PURPOSE: The purpose of this study is to compare the severity of chronic ocular complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by lamotrigine (LT) vs. trimethoprim-sulfamethoxazole (TS). METHODS: This retrospective cross-sectional study evaluated all SJS/TEN patients treated within our hospital network from 2008 to 2018. Inclusion criteria included patients with reactions identified as caused by either LT or TS, and patients with at least one ophthalmology follow up in the chronic phase (≥3 months from disease onset). Primary outcome measures included LogMAR best-corrected VA at most recent visit and the presence or absence of severe ocular complications (SOC). Secondary outcome measures included chronic ocular complication severity scores using a modified Sotozono scoring system. RESULTS: Forty-eight eyes of 24 patients were included in the study. The mean duration of follow-up was 39.50 ± 35.62 vs. 48.17 ± 33.09 months, respectively (p = 0.482). The LT group had worse average VA at the most recent visit (LogMAR VA; 0.508 vs. 0.041, p < 0.0001) and had a higher prevalence of SOCs (66.7% vs. 8.3%, p = 0.0038). The LT group scored worse on Sotozono chronic complications scores for the cornea (1.875 vs. 0.5, p = 0.0018), eyelid margin (5.583 vs.3.083, p = 0.0010), and overall condition (8.500 vs. 4.833, p = 0.0015). Sub-analyses showed that a moderate or severe acute ocular severity score was a significant predictor of chronic outcomes. CONCLUSIONS: Compared to patients with TS-induced SJS/TEN, patients with LT-induced SJS/TEN developed worse chronic ocular complications on several parameters. Future prospective studies are warranted to provide additional insight into the drug type as a predictor of chronic ocular complications.

Phencyclidine false positive induced by lamotrigine (Lamictal®) on a rapid urine toxicology screen.

BACKGROUND: This report describes two cases with unexplained positive results for phencyclidine (PCP). AIMS: This case will correlate lamotrigine (Lamictal®) use with false-positive results for PCP on a rapid urine toxicology screen. METHODS: Case 1: A 62-year-old male arrived to the emergency department in extreme psychosis. All positive results on the urine drug screen could be accounted for except PCP. A comprehensive drug screen was performed to confirm PCP use, but returned negative. PCP was ruled out as the causative agent. The reason for the PCP false positive remained unknown. Case 2: A 49-year-old female presented to the ED with a history of seizures and depression. Despite positive PCP results on a rapid urine drug screen, PCP use was ruled out due to patient presentation and comprehensive history. RESULTS: The differential diagnosis in case 1 included PCP abuse until PCP was ruled out by a comprehensive drug screen. A literature search failed to explain a reason for false-positive results. The patient in case 2 was not psychotic, but returned a positive urinalysis result for PCP. Case 2's presentation combined with a comprehensive history at the facility ruled out PCP use. Both patients were taking the anti-seizure medication lamotrigine with nothing else in common. CONCLUSION: Lamotrigine has the potential to cause false-positive results for PCP on the Bio-Rad TOX/See urine toxicology screen.