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Treatment with praziquantel in a patient with schistosomiasis and chronic renal failure
TRANSACTKX.JS OF THE ROYAL SOCIETYOF TROPICALMEDICINEAND HYGIENE,VOL. 77, No. 5, 687-688 (1983)
Treatment
with
praziquantel in a patient with chronic renal failure
687
schistosomiasis
and
P. 0. PEHRSON’,E. BENGTSSON’,H. W. DIEKMANN’ AND E. GROLL~ ‘Dept. of Infectious Diseases, Roslagstull Hospital, Karolinska Institute, Stockholm, Sweden; ‘Institut fiir Experimentelle Arzneimittelforchung der E. Merck, Darmstadt, Grafing, West Germany; 3Klinische Forschung, E. Merik, Darmstadt, West Germany
Summary
The pharmacokineticsof praziquantelin a uraemicpatient, infectedwith Schistosoma haematobium, undergoinghaemodialysis,wasstudiedby repeatedanalysesof serum,urine and dialysisfluid. The resultsindicate the possibility of treating advancedcasesof infection with S. haematobium with the normally recommendeddoses.
Observations
In a seriesof paperspublishedin 1979(DAVIS & WEGNER;DAVIS et al.; KATZ et al.; ISHIZAKIet al.; SANTOSet al.), it was shown that praziquantel (an isoquinoline-pyrazinederivative) waseffective in all speciesof schistosome parasitesaffecting man. Different doseregimenshave been suggested,most often administeredas a singleorai doseof 40 to SOmg/kg body-weight. Intensity of infection seemsto be of no imp&&e and patients with hepatosplenicdisease and cerebral involvement seemto tolerate the drug equally well. Cure ratesand eggreduction have been of the order of 90% (GILLES, 1981). Praziquantelis almostcompletely metabolizedbefore excretion and, in volunteers, more than 90% of the renal excretion was completed after 24 hours (PATZSCHKEet al.. 1979). However, to our knowledge,the useof the drug in severerenal insufficiencv (which could be one of the final consequences of irifection with S. haematobium) hasbeenstudied. We here report resultsof treating a patient -with uraemia,due to bilateral cystic kidney disease,undergoing haemodialysis. The patient was a 36-year-old immigrant from Egypt, where he had contracted infection with S. haematobium. He had beentreatedwith an antimonial preparationmorethan 20yearsago. SerumconcentraGoti of creatinine was -735 PmoVl (normal value ~120 umoY1).He wasgiven a 40 me/kg bodvweight praziqbantel’(tota1 330T,mg) in a syngleo&l dose. Repeatedserum sampleswere taken after dosing and urine was collected in six-hour samples.He underwenthaemodialysis30 hours after medication. Drug analyseswere performed by Dr. Diekmann, Merck Laboratories; using gas- chromatograph; (DIEKMANN.
1979). Results are shown in Table
I.
The serumconcentrationsare well in accordance with previous investigationsin normal subjectswith maximum about 1-Opg/ml one to three hours after intake (LEOPOLDet al., 1978; PATZSCHKEet al., 1979). The serum elimination-also correspondsto earlier values.Elimination via the kidnevs is lessthan in normal volunteers (DIEKMANN, 1$?6) and this might be due more to the rather small amountsof urine produced by our patient (14 ml/hour) than to the concentration of praziquantel in the urine. No praziquantelwasdetectablein the dialysisfluid, a fact
Table I-Quantitative determination of praziquantel in serum, urine and dialysis fluid of a patient treated with 40 mgkg bodyweight (3300 mg total dose) prior to blood dialysis
Type of sample
Hours after drug administration
Praziquantei concentration hb-4
Serum
3 6 12 24 30
1.04 I.03 0.222 0.056 0.013 d.
Urine
O-6 6-12 12-18 18-24 24-30
0.115 0.038 0.017 0.005 n.d.
Dialysis fluid
>30
n.d.
1
d = detectable but not quantifiable, n.d. = not detectable.
which could be expectedfrom the kinetic data. When the dialysisstarted, serumconcentrationwasalready very small. The data do not suggestthat the kinetics of praziquantelin bloodwerechangedin any way by the underlying kidney disease.Renal elimination of unmetabolizedpraziquantel waschangedonly slightly. The results indicate that it is possible to treat advancedcasesof infection with S. haematobium. References
Davis, A. & Wegner, D. H. G. (1979). Multicentre trials of praziquantel in human schistosomiasis: design and techniques. Bulletin of the World Health Organization, 57, 767-771. Davis, +., Biles! J. E. & Ulrich, A-M. (1979). Initial experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium. Bulletin of the World Health Organization, 57, 773-779. Diekmann, H. W. (1976). EM Bay 8440-Konzentration des unmetabolisierten Wirkstoffs im Blutplasma und Urin
PRAZIQUANTEL
688
TREATMENT
FOR
SCHISTOSOMIASIS
von Probanden nacb po. Applikation. Interner Bericht ZPD-Nr 126, E. Merck, Darmstadt. Diekmann, H. W. (1979). Quantitative determination of praziquantel in body fluids by gas liquid chromatography, EuropeanJournal of Drug Metabolism and Pharmacokinetics, 3, 139-141. Gilles, H. M. (1981). The treatment of schistosomiasis. Journal of Antimicrobial Chemotherapy, 7, 113-l 15. Ishizaki. T.. Kamo. E. & Boehme. K. (1979). Double-blind studies of tolerance to praziquantel‘in Japanese patients with Schistosoma japonicum infections. Bulletin of the World Health Organization, 57, 787-791. Katz, N., Rocha, R. S. & Chaves, A. (1979). Preliminary trials with praziquantel in human infections due to Schistosoma mansoni. B&tin of the WorldHealth Oreany izati& 57, 781-785. ’ Leopold, G., Ungethiim, Groll, E., Diekmann, H. W., Nowak, H. & Wegner, D. H. G. (1978). Clinical
Admission
to the Fellowship
of the Society
All registered medical and veterinary practitioners and othersinterestedin scientific pursuitsrelating to tropical medicine, whosequalifications are deemed satisfactoryby the Council, areeligiblefor electionas Fellows of the Society. The annualsubscriptionpayableby Fellowsis E25. The Transactions and the current Year Book of the Society are posted regularly to every Fellow whose subscriptionis not in arrear. The Transactions is available to Libraries and non-Fellows
at an annual
subscription
of f55.
Further information may be obtained from the Hon. Secretaries.MansonHouse. 26 Portland Place. London WlN 48Y, or from the’ Local Secretary of the district.
AND
CHRONIC
RENAL
FAILURE
pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. -European ‘fournal of Clinical Pharmacolow. 14. 281-291. Pa&chke, K., Putter, J., Wegner,“i. A.; Horster, F. A. & Diekmann, H. W. (1979). Serum concentrations and renal excretion in humans after oral administration of praziquantel-results of three determination methods. Eurovean Tournal of Drug Metabolism and Pharmacokinetics,- 3, 149-156. Santos, A. T., Blas, B. L., Nosenas, J. S., Portillo, G. P., Ortega,, 0. M., Hayashi, M. & Boehme, K. (1979). Prelimmary clinical trials with praziquantel in Schistosoma japonicum infections in the Philippines. Bulletin of the World Health Organization, 57, 793-799.
Accepted for publication
18th February,
1983.
CORPORATE MEMBERSHIP WITH THE ROYAL COMMONWEALTH SOCIETY, 18 NORTHUMBERLAND AVENUE, LONDON, WC2 SBJ
The Society has taken up CorporateMembership with the above Society, which haspremisesjust off Trafalgar Square.Overseas Fellows can now usethe facilitiesof this Society, when they cometo London, for a period of 21 daysin any three monthsprovided that all booking is done through the Secretary at Manson House. Fellows who wish to use these
facilities must give the Secretaryadequatenotice of their requirementsparticularly during the summer when at least two months’ notice will be required. Details of the facilities available will be sent to Fellows on request.
Treatment
with
praziquantel in a patient with chronic renal failure
687
schistosomiasis
and
P. 0. PEHRSON’,E. BENGTSSON’,H. W. DIEKMANN’ AND E. GROLL~ ‘Dept. of Infectious Diseases, Roslagstull Hospital, Karolinska Institute, Stockholm, Sweden; ‘Institut fiir Experimentelle Arzneimittelforchung der E. Merck, Darmstadt, Grafing, West Germany; 3Klinische Forschung, E. Merik, Darmstadt, West Germany
Summary
The pharmacokineticsof praziquantelin a uraemicpatient, infectedwith Schistosoma haematobium, undergoinghaemodialysis,wasstudiedby repeatedanalysesof serum,urine and dialysisfluid. The resultsindicate the possibility of treating advancedcasesof infection with S. haematobium with the normally recommendeddoses.
Observations
In a seriesof paperspublishedin 1979(DAVIS & WEGNER;DAVIS et al.; KATZ et al.; ISHIZAKIet al.; SANTOSet al.), it was shown that praziquantel (an isoquinoline-pyrazinederivative) waseffective in all speciesof schistosome parasitesaffecting man. Different doseregimenshave been suggested,most often administeredas a singleorai doseof 40 to SOmg/kg body-weight. Intensity of infection seemsto be of no imp&&e and patients with hepatosplenicdisease and cerebral involvement seemto tolerate the drug equally well. Cure ratesand eggreduction have been of the order of 90% (GILLES, 1981). Praziquantelis almostcompletely metabolizedbefore excretion and, in volunteers, more than 90% of the renal excretion was completed after 24 hours (PATZSCHKEet al.. 1979). However, to our knowledge,the useof the drug in severerenal insufficiencv (which could be one of the final consequences of irifection with S. haematobium) hasbeenstudied. We here report resultsof treating a patient -with uraemia,due to bilateral cystic kidney disease,undergoing haemodialysis. The patient was a 36-year-old immigrant from Egypt, where he had contracted infection with S. haematobium. He had beentreatedwith an antimonial preparationmorethan 20yearsago. SerumconcentraGoti of creatinine was -735 PmoVl (normal value ~120 umoY1).He wasgiven a 40 me/kg bodvweight praziqbantel’(tota1 330T,mg) in a syngleo&l dose. Repeatedserum sampleswere taken after dosing and urine was collected in six-hour samples.He underwenthaemodialysis30 hours after medication. Drug analyseswere performed by Dr. Diekmann, Merck Laboratories; using gas- chromatograph; (DIEKMANN.
1979). Results are shown in Table
I.
The serumconcentrationsare well in accordance with previous investigationsin normal subjectswith maximum about 1-Opg/ml one to three hours after intake (LEOPOLDet al., 1978; PATZSCHKEet al., 1979). The serum elimination-also correspondsto earlier values.Elimination via the kidnevs is lessthan in normal volunteers (DIEKMANN, 1$?6) and this might be due more to the rather small amountsof urine produced by our patient (14 ml/hour) than to the concentration of praziquantel in the urine. No praziquantelwasdetectablein the dialysisfluid, a fact
Table I-Quantitative determination of praziquantel in serum, urine and dialysis fluid of a patient treated with 40 mgkg bodyweight (3300 mg total dose) prior to blood dialysis
Type of sample
Hours after drug administration
Praziquantei concentration hb-4
Serum
3 6 12 24 30
1.04 I.03 0.222 0.056 0.013 d.
Urine
O-6 6-12 12-18 18-24 24-30
0.115 0.038 0.017 0.005 n.d.
Dialysis fluid
>30
n.d.
1
d = detectable but not quantifiable, n.d. = not detectable.
which could be expectedfrom the kinetic data. When the dialysisstarted, serumconcentrationwasalready very small. The data do not suggestthat the kinetics of praziquantelin bloodwerechangedin any way by the underlying kidney disease.Renal elimination of unmetabolizedpraziquantel waschangedonly slightly. The results indicate that it is possible to treat advancedcasesof infection with S. haematobium. References
Davis, A. & Wegner, D. H. G. (1979). Multicentre trials of praziquantel in human schistosomiasis: design and techniques. Bulletin of the World Health Organization, 57, 767-771. Davis, +., Biles! J. E. & Ulrich, A-M. (1979). Initial experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium. Bulletin of the World Health Organization, 57, 773-779. Diekmann, H. W. (1976). EM Bay 8440-Konzentration des unmetabolisierten Wirkstoffs im Blutplasma und Urin
PRAZIQUANTEL
688
TREATMENT
FOR
SCHISTOSOMIASIS
von Probanden nacb po. Applikation. Interner Bericht ZPD-Nr 126, E. Merck, Darmstadt. Diekmann, H. W. (1979). Quantitative determination of praziquantel in body fluids by gas liquid chromatography, EuropeanJournal of Drug Metabolism and Pharmacokinetics, 3, 139-141. Gilles, H. M. (1981). The treatment of schistosomiasis. Journal of Antimicrobial Chemotherapy, 7, 113-l 15. Ishizaki. T.. Kamo. E. & Boehme. K. (1979). Double-blind studies of tolerance to praziquantel‘in Japanese patients with Schistosoma japonicum infections. Bulletin of the World Health Organization, 57, 787-791. Katz, N., Rocha, R. S. & Chaves, A. (1979). Preliminary trials with praziquantel in human infections due to Schistosoma mansoni. B&tin of the WorldHealth Oreany izati& 57, 781-785. ’ Leopold, G., Ungethiim, Groll, E., Diekmann, H. W., Nowak, H. & Wegner, D. H. G. (1978). Clinical
Admission
to the Fellowship
of the Society
All registered medical and veterinary practitioners and othersinterestedin scientific pursuitsrelating to tropical medicine, whosequalifications are deemed satisfactoryby the Council, areeligiblefor electionas Fellows of the Society. The annualsubscriptionpayableby Fellowsis E25. The Transactions and the current Year Book of the Society are posted regularly to every Fellow whose subscriptionis not in arrear. The Transactions is available to Libraries and non-Fellows
at an annual
subscription
of f55.
Further information may be obtained from the Hon. Secretaries.MansonHouse. 26 Portland Place. London WlN 48Y, or from the’ Local Secretary of the district.
AND
CHRONIC
RENAL
FAILURE
pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. -European ‘fournal of Clinical Pharmacolow. 14. 281-291. Pa&chke, K., Putter, J., Wegner,“i. A.; Horster, F. A. & Diekmann, H. W. (1979). Serum concentrations and renal excretion in humans after oral administration of praziquantel-results of three determination methods. Eurovean Tournal of Drug Metabolism and Pharmacokinetics,- 3, 149-156. Santos, A. T., Blas, B. L., Nosenas, J. S., Portillo, G. P., Ortega,, 0. M., Hayashi, M. & Boehme, K. (1979). Prelimmary clinical trials with praziquantel in Schistosoma japonicum infections in the Philippines. Bulletin of the World Health Organization, 57, 793-799.
Accepted for publication
18th February,
1983.
CORPORATE MEMBERSHIP WITH THE ROYAL COMMONWEALTH SOCIETY, 18 NORTHUMBERLAND AVENUE, LONDON, WC2 SBJ
The Society has taken up CorporateMembership with the above Society, which haspremisesjust off Trafalgar Square.Overseas Fellows can now usethe facilitiesof this Society, when they cometo London, for a period of 21 daysin any three monthsprovided that all booking is done through the Secretary at Manson House. Fellows who wish to use these
facilities must give the Secretaryadequatenotice of their requirementsparticularly during the summer when at least two months’ notice will be required. Details of the facilities available will be sent to Fellows on request.