Paracetamol disposition in Thai patients during and after treatment of falciparum malaria

Ismail, Suzylawati; Back, David; Edwards, Geoffrey; Bangchang, Kesara Na; Karbwang, Juntra

doi:10.1007/bf00202175

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…PK–PD analysis in the current study shows a dose-dependent effect of acetaminophen on fever clearance time, whereas acetaminophen concentrations were not associated with parasite clearance rates in these artemisinin-sensitive infections. Studies that evaluated acetaminophen in uncomplicated malaria have not reported serious adverse events or hepatotoxicity attributable to acetaminophen [ 28 , 29 ]. The current study shows that administering the maximum recommended daily dosage of acetaminophen results in a moderate increase in aminotransferases, but no patient met criteria for Hy’s law for hepatotoxicity [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial

Plewes

Kingston

Ghose

et al. 2018

Clinical Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial

Plewes

Kingston

Ghose

et al. 2018

Clinical Infectious Diseases

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“…The adult dose is 1000 mg (or 15 mg/kg) every 6 h (maximum daily dose 4000 mg), given orally or via a nasogastric tube (as powdered tablets or suspension which have generally good bioavailability) (Ismail et al . ; Wilairatana et al . ).…”

Section: Section 10: Management Of Severe Malariamentioning

confidence: 97%

Severe Malaria

2014

Tropical Med Int Health

458

354

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Fever and diarrhea developed in a 34-year-old Swiss man two weeks after his return from Madagascar. Before his visit he had not taken any prophylactic antimalarial drugs. Despite self-treatment with ciprofloxacin and metronidazole, he remained febrile. He also reported hematuria and dark urine. On admission, his temperature was 39.2°C and his vital signs and mental status were normal. The abdomen was tender, and the spleen was palpable 15 cm below the costal margin. The hemoglobin level was 12.4 g per deciliter, the hematocrit was 35 percent, the white-cell count was 8500 per cubic millimeter, and the platelet count was 15,000 per cubic millimeter. The creatinine level was 2.6 mg per deciliter (234 µmol per liter), the lactate dehydrogenase level was 1920 U per liter (normal, 187 to 443), and the bilirubin level was 11.5 mg per deciliter (197 µmol per liter); the results of other liver-function tests were in the normal range. Examination of blood smears showed severe infestation with Plasmodium falciparum, with 70 to 80 percent of red cells containing up to five parasites (small ring forms) per cell (long arrow in Panel A). Other features of P. falciparum that were present included chromatin dots (arrowheads in Panel A) and appliqué forms (short arrow in Panels A and B; Wright's stain, ¬1000). About 70 percent of the neutrophils contained hemozoin (shown in a band form [long arrows] in Panel B). The patient was treated with intravenous quinine sulfate and exchange transfusions, with dramatic improvement. The degree of parasitemia fell to 65 percent after the first exchange transfusion and to 8 percent after the second. The patient's course was complicated by acute renal failure, the acute respiratory distress syndrome, and spontaneous rupture of the spleen, necessitating continuous hemofiltration, mechanical ventilation, and laparotomy with splenectomy. Despite these complications , the patient was able to return home within three months and was well at the last follow-up visit.

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“…The C MAX of paracetamol after intramuscular and oral administration (600 mg) were 11.4 and 8.52 mg/l, respectively. The lower C MAX of oral paracetamol is explained by incomplete absorption and the first-pass metabolism that occurs during absorption before paracetamol enters the systemic circulation, and the slower absorption obscuring distribution from an apparent central compartment [ 9 ]. While the pharmacokinetics of paracetamol in severe falciparum malaria have not been studied, the bioavailability of oral paracetamol may be even lower given the decrease in gastric emptying [ 33 ] and splanchnic blood flow [ 34 ] observed in severe malaria.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma samples were processed and stored at −80 °C for further analysis in Bangkok, Thailand. Paracetamol plasma concentrations were quantified using high-performance liquid chromatography, as previously described [ 9 , 10 ].…”

Section: Methodsmentioning

confidence: 99%

“…In practice, achieving therapeutic (antipyretic) plasma concentrations may be compromised, since paracetamol is often given irregularly at low doses and patients who are nauseated or unconscious will be unable to take paracetamol orally. Paracetamol given orally or via a nasogastric tube is subjected to approximately 20 % first-pass metabolism [ 9 – 11 ]. Pharmacokinetic studies show that higher dosing is required to achieve therapeutic serum concentrations when paracetamol is given by the rectal route [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria

Wattanakul

Teerapong

Plewes

et al. 2016

Malar J

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BackgroundFever is an inherent symptom of malaria in both adults and children. Paracetamol (acetaminophen) is the recommended antipyretic as it is inexpensive, widely available and has a good safety profile, but patients may not be able to take the oral drug reliably. A comparison between the pharmacokinetics of oral syrup and intramuscular paracetamol given to patients with acute falciparum malaria and high body temperature was performed.MethodsA randomized, open-label, two-treatment, crossover, pharmacokinetic study of paracetamol dosed orally and intramuscularly was conducted. Twenty-one adult patients with uncomplicated falciparum malaria were randomized to receive a single 600 mg dose of paracetamol either as syrup or intramuscular injection on day 0 followed by a single dose administered by the alternative route on day 1. Paracetamol plasma concentrations were quantified frequently and modelled simultaneously using nonlinear mixed-effects modelling. The final population pharmacokinetic model was used for dose optimization simulations. Relationships between paracetamol concentrations with temperature and parasite half-life were investigated using linear and non-linear regression analyses.ResultsThe population pharmacokinetic properties of paracetamol were best described by a two-compartment disposition model, with zero-order and first-order absorption for intramuscular and oral syrup administration, respectively. The relative bioavailability of oral syrup was 84.4 % (95 % CI 68.2–95.1 %) compared to intramuscular administration. Dosing simulations showed that 1000 mg of intramuscular or oral syrup administered six-hourly reached therapeutic steady state concentrations for antipyresis, but more favourable concentration–time profiles were achieved with a loading dose of 1500 mg, followed by a 1000 mg maintenance dose. This ensured that maximum therapeutic concentrations were reached rapidly during the first 6 h. No significant relationships between paracetamol concentrations and temperature or parasite half-life were found.ConclusionsParacetamol plasma concentrations after oral syrup and intramuscular administration in patients with acute falciparum malaria were described successfully by a two-compartment disposition model. Relative oral bioavailability compared to intramuscular dosing was estimated as 84.4 % (95 % CI 68.2–95.1 %). Dosing simulations showed that a loading dose followed by six-hourly dosing intervals reduced the time delay to reach therapeutic drug levels after both routes of administration. The safety and efficacy of loading dose paracetamol antipyretic regimens now needs to be established in larger studies.

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Paracetamol disposition in Thai patients during and after treatment of falciparum malaria

Cited by 12 publications

References 28 publications

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial

Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial

Severe Malaria

Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria

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