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Biomedical subjects

Kenneth F Ilett

Publications and source records attributed to Kenneth F Ilett.

At least 37 records · Page 2Linked to original sources
PubMed2004

The selective pulmonary vasodilatory effect of inhaled DETA/NO, a novel nitric oxide donor, in ARDS-a pilot human trial.

OBJECTIVES: To examine the effects of inhaled NONOates in patients with acute respiratory distress syndrome (ARDS). DESIGN: Case-series, phase I clinical trial. SETTING: A multidisciplinary intensive care unit in a tertiary teaching hospital. PATIENTS: Five consecutive patients with ARDS (men; age range, 47-76 years). MEASUREMENTS: DETA/NO (150 micromol) was aerosolized into the lungs of patients on mechanical ventilation via the endotracheal tube over 20 minutes. Hemodynamic parameters were measured and blood samples were taken before, during, and after inhalation. RESULTS: Compared to baseline values, pulmonary vascular resistance decreased until the end of the study period (180 minutes) while intrapulmonary shunting decreased significantly up to 45 min after DETA/NO aerosol administration. Inhaled DETA/NO had no effect on the systemic circulation (systemic blood pressure or cardiac output). CONCLUSIONS: Inhaled DETA/NO is a selective pulmonary vasodilator in patients with ARDS. However, a larger number of patients is required to confirm the findings of this pilot study.

Administration, Inhalation↗
PubMed2004

Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin) in Cambodian children and adults with malaria.

AIMS: To assess the haemodynamic, electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin (Artekin) fixed combination therapy in uncomplicated malaria. METHODS: Sixty-two Cambodians (32 children and 30 adults) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure, the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring. QT intervals were rate-corrected (QTc) using Bazett's formula. RESULTS: Artekin therapy was well tolerated and all patients responded to treatment. Average parasite and fever clearance times were 19 and 12 h, respectively. The pretreatment mean fall in systolic blood pressure on standing was 8 +/- 6 mmHg and 6-hourly measurements over 72 h showed no significant change (P = 0.48). There was a significant lengthening of the mean QTc to a maximum of 11 ms(0.5) (95% confidence interval 4-18 ms(0.5)) relative to baseline at 24 h (P = 0.003). The maximal QTc prolongation observed in any patient was 53 ms(0.5). There was a mean 0.4 mmol l(-1) reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia (plasma glucose < 3.0 mmol l(-1)) were observed at any time. CONCLUSIONS: Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults. Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine, no clinically significant cardiovascular or metabolic effects were observed.

Adolescent↗
PubMed2004

Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria.

AIMS: To study the population pharmacokinetics of piperaquine after co-administration with dihydroartemisinin in uncomplicated malaria. METHODS: The disposition of piperaquine was studied in 85 Cambodian patients with uncomplicated falciparum or vivax malaria treated with the piperaquine-dihydroartemisinin coformulation Artekin. All patients were given Artekin orally at 0, 6, 24 and 32 h with a total piperaquine dose of 32-35 mg base kg-1. Adults were given tablets while children received either tablets or a dispersible granule formulation. Patients underwent either intensive (17-19 samples) or sparse (2-5 samples) blood sampling schedules over 35 days and clinical/parasitological follow-up over > 28 days. Piperaquine in plasma was quantified by high performance liquid chromatography. RESULTS: All patients achieved fever clearance within 24 h and parasite clearance within 72 h. The 28-day cure rate was 97% in adults and 98% in children. A covariate-free two-compartment population model with first-order absorption and elimination gave the most robust representation of the plasma concentration-time data in both adults and children. In adults (n = 38), the median (interquartile range) derived pharmacokinetic descriptors CL/F, Vss/F and t1/2,z were 0.9 l h-1 kg-1 (0.79-1.02 l h-1 kg-1), 574 l kg-1(371-711 l kg-1) and 23 days (19-28 days), respectively. In children (n = 47), corresponding values were 1.8 l h-1 kg-1 (1.29-2.3 l h-1 kg-1), 614 l kg-1 (332-1205 l kg-1) and 14 days (10-18 days), respectively. CONCLUSIONS: Piperaquine is a highly lipid-soluble drug with a large Vss/F, long t1/2,z and a clearance that is markedly higher in children than in adults.

Adult↗
PubMed2004

Protein binding and alpha : beta anomer ratio of dihydroartemisinin in vivo.

AIMS: To determine the ratio of alpha : beta anomers and the protein binding of dihydroartemisinin (DHA) in vivo. METHODS: 10-[(3)H]-DHA was synthesized by reduction of artemisinin with sodium boro-[(3)H]-hydride and purified with preparative thin layer chromatography. A solution of (3)H-DHA (2000 ng in 20 micro l) was added to 2 ml whole blood from 15 healthy volunteers and 22 Vietnamese patients with falciparum or vivax malaria. The blood was centrifuged and the plasma stored at -25 degrees C until analysed by HPLC with radiochromatographic detection. Protein-free ultrafiltrate of the plasma was assayed to determine the free fraction of DHA and the in vivo ratio of alpha-DHA : beta-DHA. RESULTS: The DHA fraction unbound (mean +/- SD) was 0.068 +/- 0.032 in Vietnamese patients with falciparum malaria (n = 17), 0.065 +/- 0.009 in Vietnamese patients with vivax malaria (n = 5), 0.117 +/- 0.015 in Vietnamese volunteers (n = 7) and 0.092 +/- 0.020 in Caucasian volunteers (n = 8). The ratios of alpha-DHA : beta-DHA for the four groups were 6.3 +/- 0.9, 6.9 +/- 0.8, 6.9 +/- 0.6 and 5.4 +/- 0.8, respectively. CONCLUSIONS: DHA is approximately 93% protein-bound in patients with malaria infection and there is a preferential existence in vivo of the alpha-DHA anomer. Knowledge of this stereochemistry may be valuable in elucidation of the mechanisms of DHA action and/or toxicity, and in the synthesis of new trioxane antimalarials.

Adult↗
PubMed2004

Comparison of gentamicin dose estimates derived from manual calculations, the Australian 'Therapeutic Guidelines: Antibiotic' nomogram and the SeBA-GEN and DoseCalc software programs.

AIM: To compare gentamicin dose estimates from four predictive methods. METHODS: A retrospective study was conducted, comprising patients at Fremantle Hospital who received gentamicin therapy and had at least one gentamicin serum concentration reported. A manual calculation method, the Australian 'Therapeutic Guidelines: Antibiotic' (TGA) nomogram and the SeBA-GEN and DoseCalc software packages were compared. SeBA-GEN dose estimates were regarded as the reference standard. RESULTS: There were 64 males and 30 females with mean age of 58 +/- 16 years. In patients with moderate renal impairment (CL(Cr) = 30-60 ml min(-1); n = 21), mean dose estimates using DoseCalc and the manual calculation method were comparable to SeBA-GEN but the mean TGA nomogram dose (230 mg; 95% confidence interval 179, 281) was significantly lower than SeBA-GEN (286 mg; 261, 311; P = 0.002; one-way RM anova). In patients with mild renal impairment (CL(Cr) = 60-90 ml min(-1); n = 48), DoseCalc (392 mg; 367, 427) was comparable to SeBA-GEN (377 mg; 362, 392). Although the manual method (341 mg; 306, 376; P = 0.007) and the TGA nomogram (335 mg; 302, 368; P < 0.001) estimates were significantly lower than SeBA-GEN, the practical difference was modest. CONCLUSIONS: SeBA-GEN and DoseCalc are generally comparable for estimation of gentamicin doses in patients with renal impairment. The 'Therapeutic Guidelines: Antibiotic' nomogram is a valid approach to dosage estimation, but only when used in patients with normal renal function. Simple manual calculations are a suitable alternative in patients with renal impairment.

Anti-Bacterial Agents↗
PubMed2004

Disposition of artesunate and dihydroartemisinin after administration of artesunate suppositories in children from Papua New Guinea with uncomplicated malaria.

A detailed pharmacokinetic analysis was performed with 47 children from Papua New Guinea with uncomplicated falciparum or vivax malaria treated with artesunate (ARTS) suppositories (Rectocaps) given in two doses of approximately 13 mg/kg of body weight 12 h apart. Following an intensive sampling protocol, samples were assayed for ARTS and its primary active metabolite, dihydroartemisinin (DHA), by liquid chromatography-mass spectrometry. A population pharmacokinetic model was developed to describe the data. Following administration of the first dose, the mean maximal concentrations of ARTS and DHA were 1,085 nmol/liter at 0.9 h and 2,525 nmol/liter at 2.3 h, respectively. The absorption half-life for ARTS was 2.3 h, and the conversion half-life (ARTS to DHA) was 0.27 h, while the elimination half-life of DHA was 0.71 h. The mean common volumes of distribution for ARTS and DHA relative to bioavailability were 42.8 and 2.04 liters/kg, respectively, and the mean clearance values relative to bioavailability were 6 and 2.2 liters/h/kg for ARTS and DHA, respectively. Substantial interpatient variability was observed, and the bioavailability of the second dose relative to that of the first was estimated to be 0.72. The covariates age, sex, and alpha-thalassemia genotype were not influential in the pharmacokinetic model development; but the inclusion of weight as a covariate significantly improved the performance of the model. An ARTS suppositories dose of 10 of 20 mg/kg is appropriate for use in children with uncomplicated malaria.

Aging↗
PubMed2004

Transfer of naltrexone and its metabolite 6,beta-naltrexol into human milk.

The excretion of naltrexone and its primary metabolite 6,beta-naltrexol in breast milk from a 30-year-old lactating opiate addict undergoing oral naltrexone pharmacotherapy (5 mg/d) was studied. Concentrations of naltrexone and 6,beta-naltrexol in serial milk and plasma samples taken over a 19.3-hour period of a dose interval at steady state were measured by gas chromatography. The calculated infant dose relative to the maternal weight was 0.03% for naltrexone and 0.83% (as naltrexone equivalents) for 6,beta-naltrexol. Total relative infant dose estimated for the complete 24-hour dose interval was 1.06%. Her 6-week-old breastfed infant was healthy, achieving expected milestones, and showed no adverse effects. Only 6,beta-naltrexol was detected in infant plasma and at a very low concentration of 1.1 micro g/L. Use of naltrexone during breastfeeding should be undertaken only after an individual risk benefit analysis.

Adult↗
PubMed2003

Transfer of risperidone and 9-hydroxyrisperidone into human milk.

OBJECTIVE: To quantify the transfer of risperidone and its active metabolite 9-hydroxyrisperidone into breast milk, estimate the amount the infant receives, measure infant plasma concentrations, and clinically assess the safety of breast feeding during maternal risperidone administration. case summaries: The transfer of risperidone and 9-hydroxyrisperidone into milk was studied in 2 breast-feeding women and one woman with risperidone-induced galactorrhea. Plasma samples were available from 2 of the women and from both breast-fed infants. The milk/plasma concentration ratio determined in 2 women was <0.5 for both compounds. The calculated relative infant "doses" were 2.3%, 2.8%, and 4.7% (as risperidone equivalents) of the maternal weight-adjusted doses. Risperidone and 9-hydroxyrisperidone were not detected in the plasma of the 2 breast-fed infants studied, and no adverse effects were noted. DISCUSSION: Risperidone therapy is sometimes necessary in breast-feeding women, raising the issue of safety in the exposed infants. Our study shows that the relative infant dose is lower than the arbitrary 10% level of concern. The data provide clear guidance on infant exposure for the cases presented. CONCLUSIONS: Maternal risperidone therapy is unlikely to be a significant hazard for the breast-fed infant in the short term. Nevertheless, decisions on whether a woman may breast-feed should be made as an individual risk-benefit analysis.

Adult↗
PubMed2003

Measurement of nicotine and cotinine in human milk by high-performance liquid chromatography with ultraviolet absorbance detection.

A high-performance liquid chromatographic (HPLC) assay for the determination of nicotine and cotinine in human milk was developed using an extraction by liquid-liquid partition combined with back extraction into acid, and followed by reverse-phase chromatography with UV detection of analytes. The assay was linear up to 500 microg/l for both nicotine and cotinine. Intra- and inter-day relative standard deviations (R.S.D.) were <10% (25-500 microg/l) for both nicotine and cotinine. Limits of quantitation (LOQ) were 10 and 12 microg/l for nicotine and cotinine, respectively, while the limits of detection (LOD) were 8 and 10 microg/l for nicotine and cotinine, respectively. The mean recoveries were 79-93% (range 25-500 microg/l) for nicotine and 78-89% (range 25-500 microg/l) for cotinine. The amount of fat in the milk did not affect the recovery. We found that this method was sensitive and reliable in measuring nicotine and cotinine concentrations in milk from a nursing mother who participated in a trial of the nicotine patch for smoking cessation.

Chromatography, High Pressure Liquid↗
PubMed2003

Measurement of piperaquine in plasma by liquid chromatography with ultraviolet absorbance detection.

Piperaquine (PQ) is an antimalarial drug enjoying a resurgence of use in combination with an artemisinin derivative because of parasite resistance to standard treatments. Its pharmacokinetic properties have not been characterised. An assay for PQ in plasma was developed using solvent extraction and liquid chromatographic separation on a Waters XTerra RP(18) column, with a mobile phase of 7% acetonitrile in water (containing 0.025% trifluoroacetic acid, 0.1% NaCl and 0.008% triethylamine) and UV detection at 340 nm. The assay was linear up to 1000 microg/l. Intra- and inter-day relative standard deviations were <10% (5-500 microg/l) and <21% (5-500 microg/l), respectively. Inter-day limits of quantitation and detection were 5 microg/l and 3 microg/l, respectively. A preliminary pharmacokinetic study in a patient who received 2.56 g of PQ phosphate orally with dihydroartemisinin as four doses over 32 h found an apparent steady-state volume of distribution of 447 l/kg, an apparent oral clearance 0.93 l/h/kg and a terminal half-life of 17.3 days.

Antimalarials↗
PubMed2003

The safety of aerosolized diethylenetriamine nitric oxide adduct after single-dose administration to anesthetized piglets and multiple-dose administration to conscious rats.

Diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. It has been shown to be a selective pulmonary vasodilator in acute pulmonary hypertension. However, its potential toxicity after inhalation is unknown. This study investigated the potential toxicity of aerosolized DETA/NO after single- and multiple-dose exposure in animals. In the first part of the study, a single dose of DETA/NO (60 micromol) or placebo was aerosolized into the lungs of anesthetized piglets. Arterial methemoglobin and serum nitrite (NO2-) concentrations were measured after exposure. In the second part of the study, rats were exposed to aerosolized DETA/NO (60 micromol) or placebo for 7 days, and animals were euthanized 1, 3, 7, and 14 days after the first exposure. Serum NO2- and plasma surfactant protein B (SP-B) concentrations were measured. In both studies, acute lung inflammation was evaluated histopathologically (polymorphonuclear leucocytes (PMN) infiltration) and by measuring lung wet to dry weight ratio (LWDR). The tracheas of rats, which had the highest exposure, were further examined for ultrastructural changes using electron microscopy. In both rats and pigs, serum NO2- concentrations were elevated in all the DETA/NO-treated animals, indicating significant exposure to DETA/NO. Arterial methemoglobin was not increased by DETA/NO treatment. In the rats, plasma SP-B was not elevated by DETA/NO treatment. In addition, DETA/NO had no effects on PMN infiltration or LWDR in either animal model nor on the ultrastructure of large airways in rats. This study shows no evidence of pulmonary or hematological toxicity following single or repeated doses of DETA/NO in animals.

Administration, Inhalation↗
PubMed2003

Use of nicotine patches in breast-feeding mothers: transfer of nicotine and cotinine into human milk.

OBJECTIVE: Our objective was to assess the extent of exposure to nicotine and cotinine in breast-fed infants during maternal smoking and later during maternal use of the nicotine transdermal patch to achieve smoking cessation. METHODS: Fifteen lactating women (mean age, 32 years; mean weight, 72 kg) who were smokers (mean of 17 cigarettes per day) participated in a trial of the nicotine patch to assist in smoking cessation. Serial milk samples were collected from the women over sequential 24-hour periods when they were smoking and when they were stabilized on the 21-mg/d, 14-mg/d, and 7-mg/d nicotine patches. Nicotine and cotinine in milk were quantified by HPLC, and infant dose was calculated. Plasma concentrations of nicotine in the breast-fed infants were assessed, and the infants were also clinically assessed. RESULTS: Nicotine and cotinine concentrations in milk were not significantly different between smoking (mean of 17 cigarettes per day) and the 21-mg/d patch, but concentrations were significantly lower (P <.05) when patients were using the 14-mg/d and 7-mg/d patches than when smoking. There was also a downward trend in absolute infant dose (nicotine equivalents) from smoking or the 21-mg patch through to the 14-mg and 7-mg patches (P <.05 at both 14-mg and 7-mg doses, compared with smoking). Milk intake (shown as median and 25th to 75th percentile) by the breast-fed infants was similar while their mothers were smoking (585 mL/d [507-755 mL/d]) and subsequently when their mothers were using the 21-mg (717 mL/d [504-776 mL/d]), 14-mg (731 mL/d [535-864 mL/d]), and 7-mg (619 mL/d [520-706 mL/d]) patches (chi(2) = 3.19, P =.364). CONCLUSIONS: We conclude that the absolute infant dose of nicotine and its metabolite cotinine decreases by about 70% from when subjects were smoking or using the 21-mg patch to when they were using the 7-mg patch. In addition, use of the nicotine patch had no significant influence on the milk intake by the breast-fed infant. Undertaking maternal smoking cessation with the nicotine patch is, therefore, a safer option than continued smoking.

Administration, Cutaneous↗
PubMed2003

Pseudoephedrine: effects on milk production in women and estimation of infant exposure via breastmilk.

AIMS: To assess the effects of pseudoephedrine on breast blood flow, temperature and milk production, and to estimate the likely infant dose during breastfeeding. METHODS: Eight lactating women (mean age 35 years and weight 69 kg) participated in a single-blind randomized crossover study of 60 mg pseudoephedrine hydrochloride vs placebo. Breast blood flow and surface temperature were measured from 0 to 4 h following the dose, and change in plasma prolactin was measured as the difference between predose and 1 h postdose concentrations. Milk production was measured for 24 h following placebo and pseudoephedrine. Infant dose of pseudoephedrine for a 60-mg dose administered four times daily to the mother was quantified as the product of average steady-state drug concentration in milk and an estimated milk production rate of 0.15 l x kg(-1) x day(-1) and expressed relative to the maternal weight-adjusted dose. RESULTS: There were no physiologically significant changes in breast blood flow or temperature between the placebo and pseudoephedrine periods. The mean change in plasma prolactin was slightly (13.5%), but not significantly lower (t = 1.245, P = 0.253) after pseudoephedrine (1775 mU x l(-1)) compared with placebo (2014 mU x l(-1)). However, the mean milk volume was reduced by 24% from 784 ml x day(-1) in the placebo period to 623 ml x day(-1) in the pseudoephedrine period (difference between means 161 ml x day(-1) (95% CI: 63, 259 ml x day(-1)); t = 3.9, P = 0.006). Assuming maternal intake of 60 mg pseudoephedrine hydrochloride four times daily, the estimated infant dose of pseudoephedrine was 4.3% (95% CI, 3.2, 5.4%) of the weight-adjusted maternal dose. CONCLUSIONS: A single dose of pseudoephedrine significantly reduced milk production. This effect was not attributable to changes in blood flow, but depression of prolactin secretion may be a contributing factor. At the maximum recommended pseudoephedrine doses, the calculated infant dose delivered via milk was < 10% of the maternal dose, and is unlikely to affect the infant adversely. The ability of pseudoephedrine to suppress lactation suggests a novel use for the drug.

Adrenergic alpha-Agonists↗
PubMed2003

Diethylenetriamine nitric oxide adduct relaxes precontracted mouse tracheal smooth muscle.

1. Inhaled diethylenetriamine nitric oxide adduct (DETA/NO) has been shown to be a selective pulmonary vasodilator in animal and human studies. The aims of the present study were to investigate the effect of DETA/NO on mouse precontracted isolated tracheal smooth muscle preparations and to determine the active component of this compound. 2. Mouse isolated tracheal smooth muscle rings were precontracted with carbachol (10-7 mol/L). Changes in isometric tension were recorded after cumulative addition of DETA (30-300 micromol/L; n = 6), DETA/NO (30-300 micromol/L; n = 9) or diluent control (n = 3). In addition, some preparations (n = 5) were pretreated with the soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]-oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ; 30 micromol/L) before precontraction and exposure to DETA/NO. 3. Addition of DETA/NO caused a concentration-dependent relaxation of tracheal smooth muscle at 100 and 300 micromol/L, with an EC25%R of 109 micromol/L (95% confidence interval 72.6-164 micromol/L). The nucleophile amine carrier DETA had no effect on isometric tension. However, the relaxant effect of DETA/NO was completely abolished by pretreatment with ODQ. 4. We conclude that DETA/NO induces a concentration-dependent relaxation of mouse carbachol-contracted isolated tracheal smooth muscle that is mediated by NO released from DETA/NO via the activation of sGC.

Animals↗
PubMed2003

Investigation of target plasma concentration-effect relationships for olanzapine in schizophrenia.

Olanzapine is an atypical antipsychotic effective in the treatment of schizophrenia. The present study has examined the potential use of target concentration monitoring of olanzapine in plasma as a marker of clinical response and an aid in patient management. Fifty-three patients (mean age 32 years; 40 M, 13 F) with a DSM-IVR diagnosis of schizophrenia completed a 6-week trial of oral olanzapine. Participants received once-daily olanzapine, and their psychotic symptoms were measured with the PANSS (Positive and Negative Symptom Scale) on admission and again after 6 weeks. Responders were classified as having a >/=20% decrease in PANSS scores. Plasma olanzapine was quantified by high-performance liquid chromatography. Receiver operator characteristic (ROC) curve analysis was used to identify a break point in plasma olanzapine that might serve as a surrogate for PANSS classification, and the two methods were compared using the McNemar chi2 test. After 6 weeks the median olanzapine dose was 15 mg/d (range 5-30 mg/d), and the mean plasma olanzapine was 32 micrograms/L at a mean of 13.5 hours after dose. With the PANSS (total), there were 42 responders and 11 nonresponders. ROC curve analysis for total PANSS identified a break point at 23 micrograms/L plasma olanzapine, with the proportions of responders and nonresponders identified by PANSS and the plasma break point being similar. Similar break points were found for the positive, negative, and global PANSS subscores. Nevertheless, these relationships were very modest, and at best the target plasma olanzapine concentration identified only 20% more responders than nonresponders. We suggest that plasma olanzapine monitoring can be used for dose-response optimization, but only to complement the normal clinical evaluation process.

Adult↗
PubMed2003

Safety and therapeutic efficacy of artesunate suppositories for treatment of malaria in children in Papua New Guinea.

BACKGROUND: Although suppositories of artemisinin derivatives may be a valuable option for treatment of malaria in children when circumstances prevent oral and parenteral therapy, few confirmatory data have been published. METHODS: We assessed the safety and efficacy of rectal artesunate in 47 children ages 5 to 10 years with uncomplicated malaria acquired in a hyperendemic area of Papua New Guinea. Thirty were symptomatic and had Plasmodium falciparum parasitemia >2000/microl (Group 1), 12 had and either a parasitemia <2000/microl or minimal/no symptoms (Group 2) and 5 had Plasmodium vivax (Group 3). Each child received rectal artesunate 10 to 15 mg/kg at 0 and 12 h. After monitoring for 24 h, chloroquine plus sulfadoxine/pyrimethamine was given, and the patient discharged. RESULTS: Artesunate suppositories were well-tolerated. After 24 h only one child (from Group 1) had persistent parasitemia, and only one (from Group 3) had not defervesced. These two children received intramuscular quinine and recovered uneventfully. Three Group 2 children redeveloped fever and tachycardia at 24 h, but each responded to simple supportive measures and remained aparasitemic. CONCLUSIONS: Intrarectal artesunate is safe, effective initial treatment for uncomplicated malaria in children. A transient fever spike can sometimes occur after parasite clearance. We recommend that children with uncomplicated malaria receive two doses of > or =10 mg/kg rectal artesunate within the first 24 h.

Animals↗
PubMed2003

Penetration of dihydroartemisinin into cerebrospinal fluid after administration of intravenous artesunate in severe falciparum malaria.

Penetration of cerebrospinal fluid (CSF) by artesunate and DHA was assessed in six adults with cerebral or severe malaria. Lumbar punctures were performed on admission and during convalescence, at 15 min (patient 1), 30 min (patient 2), 45 min (patient 3), 60 min (patient 4), 90 min (patient 5), and 120 min (patient 6) after intravenous administration of 120 mg of artesunate. No artesunate was detectable in CSF. In both studies, DHA levels in CSF increased with time while dihydroartemisinin levels in plasma fell. Dihydroartemisinin might accumulate in CSF during frequent artesunate dosing.

Adolescent↗