. (1983). High-performance liquid chromatographic determination of galanthamine, a long-acting anticholinesterase drug, in serum, urine, and bile. Journal of Chromatography, A, 275(2), 345-353. DOI: 10.1016/S0378-4347(00)84380-7
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SUMMARYThe anticholinesterase drug galanthamine is obtained from alkalinized serum by repeated liquid--liquid extraction. The resulting extract is approximately 100 times concentrated with respect to the original sample. Quantitative determination of galanthamine is performed with normal-phase liquid chromatography using a mixture of dichloromethane-n-hexane and ethanolamine as an eluent. Phenacetin is used as internal standard. The absorption of the column effluent is monitored at 235 nm. No endogenous sources of interference have been observed. A galanthamine serum level of 5 ng/ml is found as the minimum detectable concentration; the coefficient of variation at this level is 37.8% (n = 4). For the assay of galanthamine in the concentration range 10-100 ng/ml, standard deviations vary between 18.9 and 2.5% (n = 32).
The pharmacokinetics of the long-acting anticholinesterase drug, galanthamine, were investigated in eight patients. After i.v. injection of 0.3 mg kg-1, the decrease in the serum concentration of galanthamine followed a biexponential curve. The serum concentration decreased rapidly from 543 +/- 47 ng ml-1 to 128 +/- 14 ng ml-1 between 2 and 30 min with a T1/2 alpha of 6.42 +/- 2.15 min, and then declined more slowly with a T1/2 beta of 264 +/- 28 min. Total serum clearance of galanthamine amounted to 5.37 +/- 0.87 ml min-1 kg-1, and the renal clearance was 1.36 +/- 0.10 ml min-1 kg-1. The cumulative urinary excretion of galanthamine between 0 and 48 h after injection amounted to 28.0 +/- 5.4% of the administered dose. The biliary excretion of galanthamine during 24 h amounted to 0.2 +/- 0.1% of the dose. There was no evidence of glucuronide or sulphate conjugation of galanthamine.
T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 374;5 nejm.org February 4, 2016
469Images in Clinical Medicine D uring a 3-month elective in Uganda, a 24-year-old Dutch medical student swam in the Nile River. Two months after his return, he presented to a clinic with a 7-week history of a nonproductive cough and malaise, as well as a 2-week history of diarrhea and nonpruritic rash. Physical examination and diagnostic testing revealed multiple small papules on the trunk (Panel A), eosinophilia (3.0×10 9 eosinophils per liter), mildly elevated liver-function values, and several ill-defined nodular infiltrates on the chest radiograph (Panel B, arrows). Tests were positive for antibodies against schistosomal worms but not for antibodies against schistosomal eggs. Analysis of a skin-lesion biopsy specimen revealed nonspecific eosinophilic infiltrates without eggs. These findings support the diagnosis of acute schistosomiasis, or Katayama fever. Katayama fever is thought to be due to an immunologic response to the antigens present during the maturation process of the schistosomal worm. It typically manifests 2 to 10 weeks after exposure as fever, cough, urticarial rash, and fatigue, accompanied by eosinophilia and transient pulmonary infiltrates. Treatment with a single oral dose of praziquantel, preferably given after the acute stage, typically results in complete cure, as was seen in this patient.
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