{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:38:23Z","timestamp":1789911503905,"version":"4.0.1"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[1996,7,1]],"date-time":"1996-07-01T00:00:00Z","timestamp":836179200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1996,7]]},"abstract":"<jats:p>Plasmodium berghei-infected mice died with low levels of parasitemia after repeated intraperitoneal administration (five times at 15 mg kg of body weight-1 every other day) of the in vitro active antimalarial acyclic nucleoside phosphonate (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA]. Toxicological studies showed that the main cause of death resulted from (S)-HPMPA-induced nephrotoxicity. Although concomitant intraperitoneal administration of the tubular epithelium transport blocker probenecid prevented (S)-HPMPA-induced toxicity, mice eventually died with a high level of parasitemia, despite repeated administration of high doses of (S)-HPMPA. The short half-life of (S)-HPMPA in plasma combined with the insusceptibility of the nonreplicative stages of the parasite to (S)-HPMPA could explain this failure to eradicate all parasites. Indeed, a low but sustained (calculated) level of 200 nM (S)-HPMPA in plasma completely cured P. berghei-infected mice. However, these mice, which received a total dose of only 28 mg kg-1 administered via osmotic pumps for 7 days, died because of the toxicity of the drug. These findings indicate that nephrotoxicity hinders the use of (S)-HPMPA as a drug against blood stage parasites. An alternative application of (S)-HPMPA as a potent prophylactic drug is discussed.<\/jats:p>","DOI":"10.1128\/aac.40.7.1584","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:25:57Z","timestamp":1539044757000},"page":"1584-1588","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Antimalarial and toxic effects of the acyclic nucleoside phosphonate (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine in Plasmodium berghei-infected mice"],"prefix":"10.1128","volume":"40","author":[{"given":"L J","family":"Smeijsters","sequence":"first","affiliation":[{"name":"Department of Parasitology, Faculty of Veterinary Medicine, University of Ultrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Nieuwenhuijs","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Veterinary Medicine, University of Ultrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R C","family":"Hermsen","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Veterinary Medicine, University of Ultrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G M","family":"Dorrestein","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Veterinary Medicine, University of Ultrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F F","family":"Franssen","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Veterinary Medicine, University of Ultrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P","family":"Overdulve","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Veterinary Medicine, University of Ultrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.40.7.1584","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.40.7.1584","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:10:22Z","timestamp":1645474222000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.40.7.1584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,7]]},"references-count":0,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1996,7]]}},"alternative-id":["10.1128\/AAC.40.7.1584"],"URL":"https:\/\/doi.org\/10.1128\/aac.40.7.1584","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,7]]},"assertion":[{"value":"1996-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}