title: Estimation of Monocrotophos renal elimination half-life in humans.
abstract: BACKGROUND
  Monocrotophos, implicated in about 1/4th of organophosphate poisonings in our centre, is associated with the highest mortality (24%). Yet data on its pharmacokinetics in humans is limited. We estimated the renal elimination half-life of monocrotophos.
  
  
  METHODS
  Consecutive patients presenting with monocrotophos overdose over a 2-month period who had normal renal function were recruited. Monocrotophos in plasma and urine were quantitated by high-performance liquid chromatography. Urine was obtained from catheterised samples at 0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 h. Plasma specimens were collected at the time of admission, and at the midpoint of the urine sample collections at 1, 3, 5, 7, 10, 15 and 21 h. Renal elimination half-life was calculated from the cumulative amount excreted in the urine.
  
  
  RESULTS
  The cohort of 5 male patients, aged 35.8 ± 2.94 years, presented with typical organophosphate (cholinergic) toxidrome following intentional monocrotophos overdose. All patients required mechanical ventilation; one patient died. Plasma data was available from 5 patients and urine data from 3 patients. The median renal elimination half-life was 3.3 (range: 1.9-5.0 h). Plasma monocrotophos values, as natural log, fell in a linear fashion up to around 10 h after admission. After the 10-hour period, there was a secondary rise in values in all the 3 patients in whom sampling was continued after 10 h.
  
  
  CONCLUSIONS
  A renal elimination half-life of 3.3 h for monocrotophos is consistent with a water-soluble compound which is rapidly cleared from the plasma. The secondary rise in plasma monocrotophos values suggests possible re-distribution. Determining the elimination profile of this compound will help develop better strategies for treatment.
authors.affiliation: Department of Clinical Biochemistry, Christian Medical College , Vellore , India.
authors.forename: Arun
authors.initials: A
authors.lastname: Jose
authors.forename: Ratnasamy
authors.initials: R
authors.lastname: Selvakumar
authors.forename: John Victor
authors.initials: JV
authors.lastname: Peter
authors.forename: Gunasekaran
authors.initials: G
authors.lastname: Karthik
authors.forename: Denise Helen
authors.initials: DH
authors.lastname: Fleming
authors.forename: Jude Joseph
authors.initials: JJ
authors.lastname: Fleming
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007362:Intensive Care Units; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008999:Monocrotophos / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D062025:Organophosphate Poisoning / Q000097:blood* / Q000652:urine*; D065667:Renal Elimination; D013048:Specimen Handling
chemical_list: D008999:Monocrotophos
keywords: Human; Organophosphate; Pharmacokinetics; Renal clearance