Biomedical subjects

S Valind

Publications and source records attributed to S Valind.

At least 19 recordsLinked to original sources

PubMed2006

Reference values for respiratory system impedance by using impulse oscillometry in children aged 2-11 years.

The forced oscillation technique makes it possible to evaluate the mechanical properties of the respiratory system with a minimum of cooperation. The method is therefore especially useful in children. Impulse oscillometry (IOS) is a commercially available version of this technique. There is, as yet, limited information on reference values for IOS in children. The aim of this study was to extend the reference values for IOS variables and to study their correlation with height, weight and age in healthy children. A sample (n = 360) of children (age 2.1-11.1 years) was measured by using impulse oscillometry (IOS; Jaeger, Würzburg, Germany). The sample was based on children attending kindergarten in Finland and children attending primary school in Sweden. Measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs) and the resonance frequency (Fr) were made. All variables were related to body height. Most of them were also weakly related to weight. Reference equations for children (height 90-160 cm) are presented.

Age Factors↗

PubMed2001

Occurrence and prognostic significance of ventricular arrhythmia is related to pulmonary function: a study from "men born in 1914," Malmö, Sweden.

BACKGROUND: Reduced lung function has been associated with increased rates of myocardial infarction. Whether the occurrence and prognostic significance of ventricular arrhythmia is related to lung function is largely unknown. METHODS AND RESULTS: We performed a population-based study of 68-year-old men without a history of stroke or myocardial infarction; 402 men participated. Mortality and coronary events (fatal or nonfatal) were studied in relation to ventricular arrhythmia during 24 hours, percentage of the predicted forced expiratory volume (FEV1(%pred)), vital capacity (VC(%pred)), and the FEV/VC ratio. During 14 years of follow-up, 181 men died and 87 experienced a coronary event. Occurrence of frequent or complex ventricular arrhythmia (Lown class 2 to 5) was significantly and inversely associated with FEV1(%pred). Men with Lown class 2 to 5 and a low FEV1(%pred) (below median) had significantly higher mortality (71.5 versus 26.8 per 1000 person-years; P<0.0001) and coronary event rates (37.7 versus 18.0; P=0.02) than men with Lown class 2 to 5 and a high FEV1(%pred). These associations remained significant after adjustments for potential confounders (mortality: relative risk [RR], 2.91; 95% CI,1.68 to 5.04; coronary events: RR, 2.16; 95% CI, 1.07 to 4.37). In men without frequent or complex arrhythmia (Lown 0 to 1), a low FEV1(%pred) was not significantly associated with mortality (RR, 1.37; 95% CI, 0.92 to 2.05) or coronary events (RR, 1.24; 95% CI, 0.67 to 2.27) after adjustments for confounders. The FEV/VC ratio showed similar associations with arrhythmia, mortality, and coronary events. CONCLUSIONS: Lung function is inversely associated with the occurrence of ventricular arrhythmia. The increased incidence of myocardial infarction and death associated with arrhythmia was mainly limited to men with a low FEV1(%pred) or FEV/VC. We suggest that lung function should be considered when assessing the prognostic significance of ventricular arrhythmia.

Aged↗

PubMed2001

Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment.

The objective of this study was to assess whether reduced glucose metabolism (rCMRGlu) and cognitive functioning could predict development of Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Twenty MCI patients underwent baseline and follow-up investigations of rCMRGlu, as measured by PET, and cognitive function measured by neuropsychological test assessments. Subjects were clinically followed up with an average interval of 36.5 months. Two groups were obtained after the second clinical assessment. Nine patients were diagnosed as AD and classified as progressive MCI (P-MCI), whereas 11 patients remained clinically stable and were classified as stable MCI (S-MCI). There were no differences in demographic variables or baseline MMSE between the two subgroups. Logistic regression indicated the two variables that most effectively predicted future development of AD were rCMRGlu from the left temporoparietal area and performance on the block design. These combined measures gave an optimal 90% correct classification rate, whereas only rCMRGlu or neuropsychology alone gave 75% and 65% correct classification, respectively. Measures of temporoparietal cerebral metabolism and visuospatial function may aid in predicting the evolution to AD for patients with MCI.

Aged↗

PubMed2001

Asymptomatic leg and carotid atherosclerosis in smokers is related to degree of ventilatory capacity: longitudinal and cross-sectional results from 'Men born in 1914', Sweden.

Although smoking is associated with cardiovascular disease (CVD), many individuals remain healthy after many years of smoking. The population based cohort 'Men born in 1914' was used to investigate whether the occurrence of non-invasively detected atherosclerosis among smokers is associated with lung function [(i.e. height-adjusted forced expiratory volume during 1 s (FEV1.0) and vital capacity (VC)]. Two hundred and seven smokers without history of CVD were examined with spirometry and calf plethysmography at 55 years, and with spirometry, ankle-arm blood pressure recordings and ultrasound examinations of the carotid arteries at 68 years. Eighty-three men had atherosclerosis defined as carotid stenosis >30% or ankle-arm index <0.9. FEV1.0 and VC were both at 55 years (longitudinally) and at 68 years (cross-sectionally) lower among men with atherosclerosis at 68 years (55 years: FEV1.0, 3.2+/-0.6 vs. 3.4+/-0.5 l; P=0.02; VC, 4.2+/-0.5 vs. 4.4+/-0.5 l; P=0.02; 68 years: FEV1.0, 2.6+/-0.6 vs. 2.9+/-0.7 l; P=0.004; VC, 3.8+/-0.6 vs. 4.0+/-0.6; P=0.009, for men with and without atherosclerosis). The longitudinal and cross-sectional associations between FEV1.0, VC and atherosclerosis remained significant after adjustments for several potential confounders (tobacco consumption at 55 and 68 years, hypertension, diabetes, alcohol consumption at 68 years, and pulse wave amplitude as a measure of degree of atherosclerosis at 55 years). We conclude that the risk of developing atherosclerosis is associated with the degree of ventilatory capacity. The results suggest that in smokers, reduced lung function is a marker of susceptibility for atherosclerosis.

Aged↗

PubMed2001

Myocardial insulin-mediated glucose uptake and left ventricular geometry.

Whole-body insulin sensitivity has been shown to be impaired in subjects with increased left ventricular relative wall thickness (RWT) and in hypertensive subjects with left ventricular hypertrophy, but the relation between myocardial insulin sensitivity and RWT or left ventricular mass index (LVMI) in normotension is not known. We measured myocardial and skeletal muscle glucose uptake with [18F]fluorodeoxyglucose and positron emission tomography during hyperinsulinemic euglycemic clamp in nine men with wide ranges of echocardiographic RWT and LVMI. The subjects were male, 72-74 years old, normotensive and free from medication or history of heart disease. RWT correlated inversely with skeletal muscle glucose uptake (r = -0.69, p = 0.04), borderline significantly directly with myocardial glucose uptake (r = 0.62, p = 0.07), and directly with the ratio between myocardial and skeletal muscle glucose uptake (r = 0.77, p = 0.02) during hyperinsulinemic euglycemic clamp. LVMI was not related to insulin-mediated myocardial or skeletal muscle glucose uptake or the ratio between myocardial and skeletal muscle glucose uptake. In conclusion, RWT was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in healthy normotensive elderly men, whereas LVMI was not related to myocardial or skeletal muscle insulin sensitivity.

Aged↗

PubMed2001

Increased incidence of myocardial infarction and stroke in hypertensive men with reduced lung function.

BACKGROUND AND OBJECTIVE: Although hypertension is associated with increased cardiovascular risk, many individuals remain free from disease. This study is aimed to investigate whether this variation in individual susceptibility is associated with lung function. DESIGN: Population-based prospective cohort study. PARTICIPANTS: 'Men born in 1914', Malmö, Sweden. Subjects (n = 639) were examined and considered free from prevalent cardiovascular disease at age 55 years. MAIN OUTCOME MEASURES: Mortality, fatal and non-fatal stroke and cardiac events (fatal or non-fatal myocardial infarction) during 28-years follow-up. RESULTS: Of the men, 467 had normal blood pressure and 172 (27%) had hypertension (> or = 160/95 mmHg or treatment for hypertension). Hypertensive men with height-adjusted forced expiratory volume during 1 s (FEV1.0) below median had significantly higher rates of stroke (13.4 versus 5.8/1,000 person-years), cardiac events (27.1 versus 12.8/1,000 person-years) and all cause mortality (52.5 versus 28.6/1,000 person-years) than hypertensive men with high FEV1.0. These differences remained statistically significant after adjustment for potential confounders. Men with normal blood pressure and FEV1.0 below median had higher rates of stroke (5.4 versus 4.2/1,000 person-years), cardiac events (13.3 versus 11.6/1,000 person-years) and all cause mortality (29.9 versus 21.2/1,000 person-years) than men with normal blood pressure and high FEV1.0. After adjustments for potential confounders, FEV1.0 was significantly associated with mortality among men with normal blood pressure, whereas the associations with stroke and cardiac events did not reach significance. CONCLUSION: The incidence of cardiovascular disease and death associated with hypertension is increased among men with reduced lung function. The synergistic interaction between hypertension and lung function was independent of smoking and other potential confounders.

Cohort Studies↗

PubMed2001

Blood pressure increase between 55 and 68 years of age is inversely related to lung function: longitudinal results from the cohort study 'Men born in 1914'.

BACKGROUND: Although age is associated with increasing blood pressure, there is a substantial heterogeneity within a certain birth cohort. Whether increase in systolic and diastolic blood pressure is related to pulmonary function is largely unknown. OBJECTIVE: To study blood pressure elevation between 55 and 68 years of age in relation to vital capacity (VC) and forced expiratory volume (FEV1.0) at 55. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 375 men without antihypertensive medication at baseline. MAIN OUTCOME MEASURE: Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) over 13 years. RESULTS: Blood pressure increase between 55 and 68 years was highest among men who at 55 years had low vital capacity. Average increase in systolic blood pressure for men with vital capacity in the first, second, third and fourth quartile was 20.4, 18.7, 16.5 and 11.1 mmHg, respectively (P for trend = 0.005). Average increase in diastolic blood pressure was 10.6, 9.9, 9.0 and 6.3 mmHg, respectively (P= 0.02). The trends remained statistically significant after adjustments for baseline blood pressure, tobacco consumption, smoking cessation between 55 and 68, weight change between 55 and 68, physical activity and diabetes. Further analysis showed that the relationships could be found among men with blood pressures < or = 140/ 90 mmHg at baseline, whereas no significant association was found for men whose baseline SBP or DBP exceeded 140/90 mmHg. FEV1.0 showed similar associations with change in blood pressure. CONCLUSION: Lung function is inversely associated with future blood pressure increase. It is suggested that this association could contribute to the relationships between lung function and incidence of cardiovascular disease.

Aged↗

PubMed2000

[Rapid increase of the use of PET in cancer investigation--but Sweden lags behind].

Glucose consumption in tissue can be measured using positron emission tomography (PET) and 18F-deoxyglucose (18FDG). Malignant tumors rely largely on anaerobic glycolysis and show very rapid glucose consumption, and can therefore be imaged using PET and 18FDG. PET has been shown to be useful in the evaluation of patients with e.g. lung cancer, colo-rectal cancer, malignant melanoma and malignant lymphoma, in terms of both diagnostic accuracy and cost-effectiveness. The clinical use of PET for workup of cancer patients is increasing rapidly in North America as well as in the European Union, but Sweden is lagging behind.

Fluorine Radioisotopes↗

PubMed2000

[Rapid increase of the use of PET in cancer investigation--but Sweden lags behind].

Deoxyglucose↗

PubMed2000

Respiratory decline in smokers and ex-smokers--an independent risk factor for cardiovascular disease and death.

BACKGROUND AND OBJECTIVE: Although smoking is associated with an increased incidence of cardiovascular disease and death, many smokers remain healthy after many years of smoking. Our objective was to assess whether this variation is related to rate of decline of respiratory function. DESIGN: This was a population-based cohort study, its subjects being men born in 1914 from Malmö, Sweden. METHODS: All 291 smokers who since the baseline examination in 1969 had remained in Malmö were invited to a follow-up examination in 1982. Of the 242 participants, 199 men without history of myocardial infarction or stroke were included in the study. Eighty-four of them had quit smoking. The incidence of cardiovascular disease and death during 14 years was studied in relation to the decline in lung function [forced expiratory volume during 1 second (FEV1.0) and vital capacity] between 55 and 68 years of age. RESULTS: Fifty-nine (51%) smokers and 43 (51%) ex-smokers died. Forty-four (38%) smokers and 29 (35%) ex-smokers suffered a cardiovascular event. The mortality rate among smokers in the high, middle and low thirds with regard to the decline in FEV1.0 was 66.5, 44.0, and 37.6, respectively, per 1000 person-years (P for trend = 0.04). The corresponding figures in ex-smokers were 88.7, 42.0, and 35.1 (P for trend = 0.002). The cardiovascular event rate among smokers in these three groups was 56.0, 41.0, and 22.7 events, respectively, per 1000 person-years (P for trend = 0.01). The association remained significant after adjustments for potential confounders. A change in vital capacity was associated with a similar pattern of disease and death. CONCLUSION: Although smoking is associated with an accelerated respiratory decline, there are marked differences between smokers. The increased cardiovascular event and death rates among those whose lung function declined the most suggests that the change in respiratory function can be used as a measure of individual susceptibility.

Age Factors↗

PubMed1999

Neuroimaging study in autosomal dominant cerebellar ataxia, deafness, and narcolepsy.

Four patients affected with autosomal dominant cerebellar ataxia, deafness, and narcolepsy underwent brain CT and MRI. Radiologic findings were supratentorial atrophy (more pronounced than infratentorial atrophy), pronounced dilatation of the third ventricle, low T2 signal intensity in the basal ganglia, loss of cerebral cortex-white matter differentiation, and periventricular high-signal rims. 2-[18F]Fluoro-2-deoxy-D-glucose PET was done with one patient, without specific findings. Genetic analyses excluded SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, DRPLA, and huntingtin gene mutations.

Adolescent↗

PubMed1999

Glucose utilisation in the lungs of septic rats.

Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose ((18)FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of (18)FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. (18)FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions.

Animals↗

PubMed1999

Kinetic analysis of 52Fe-labelled iron(III) hydroxide-sucrose complex following bolus administration using positron emission tomography.

Kinetic analysis of a single intravenous injection of 100 mg iron(III) hydroxide-sucrose complex (Venofer) mixed with 52Fe(III) hydroxide-sucrose as a tracer was followed for 3-6 h in four generally anaesthetized, artificially ventilated minipigs using positron emission tomography (PET). The amount of injected radioactivity ranged from 30 to 200 MBq. Blood radioactivity, measured by PET in the left ventricle of the heart, displayed a fast clearance phase followed by a slow one. In the liver and bone marrow a fast radioactivity uptake occurred during the first 30 min, followed by a slower steady increase. In the liver a slight decrease in radioactivity uptake was noted by the end of the study. A kinetic analysis using a three-compartment (namely blood pool, reversible and irreversible tissue pools) model showed a fairly high distribution volume in the liver as compared with the bone marrow. In conclusion, the pharmacokinetics of the injected complex was clearly visualized with the PET technique. The organs of particular interest, namely the heart (for blood kinetics), liver and bone marrow could all be viewed by a single setting of a PET tomograph with an axial field of view of 10 cm. The half-life (T1/2) of 52Fe (8.3 h) enables a detailed kinetic study up to 24 h. A novel method was introduced to verify the actual 52Fe contribution to the PET images by removing the interfering radioactive daughter 52mMn positron emissions. The kinetic data fitted the three-compartment model, from which rate constants could be obtained for iron transfer from the blood to a pool of iron in bone marrow or liver to which it was bound during the study period. In addition, there was a reversible tissue pool of iron, which in the liver slowly equilibrated with the blood, to give a net efflux from the liver some hours after i.v. administration. The liver uptake showed a relatively long distribution phase, whereas the injected iron was immediately incorporated into the bone marrow. Various transport mechanisms seem to be involved in the handling of the injected iron complex.

Bone Marrow↗

PubMed1999

Pharmacokinetics and red cell utilization of iron(III) hydroxide-sucrose complex in anaemic patients: a study using positron emission tomography.

The pharmacokinetics of a single intravenous injection of 100 mg iron hydroxide-sucrose complex labelled with a tracer in the form of 52Fe/59Fe was followed in six anaemic patients for a period ranging from 6 to 8 3 h using positron emission tomography (PET). Red cell utilization of the labelled iron was followed for 4 weeks. PET data showed radioactive uptake by the liver, spleen and bone marrow. The uptake by the macrophage-rich spleen demonstrated the reticuloendothelial uptake of this iron preparation, with subsequent effective release of that iron for marrow utilization. Red cell utilization, followed for 4 weeks, ranged from 59% to 97%. The bone marrow influx rate constant was independent of blood iron concentration, indicating non-saturation of the transport system in bone marrow. This implied that higher doses of the iron complex can probably be used in the same setting. A higher influx rate into the marrow compared with the liver seemed to be consistent with higher red cell utilization. This would indicate that early distribution of the injected iron complex may predict the long-term utilization.

Adult↗

PubMed1999

Regional VA/Q ratios in man using 133Xe and single photon emission computed tomography (SPECT) corrected for attenuation.

We describe a technique to obtain non-invasively regional pulmonary ventilation-perfusion ratios (VA/Q) using single photon emission computed tomography (SPECT) and continuous infusion of 133Xe. Single photon transmission tomography was used for attenuation correction, for delineation of the lungs and for VA/Q calculations. Data are presented for six normal subjects and compared to those for two patients with moderate chronic obstructive pulmonary disease (COPD). The mean VA/Q for the whole lung of the normal subjects ranged from 0.49 to 0.65, group mean 0.56 +/- 0.07 (1 SD), and there was no significant difference between the right and left lung. The consistently too low VA/Q values are related to the inability to measure regional blood volume and the low resolution of the scintillation camera, giving an under-estimation of tracer input. For the normal subjects, the dispersion of VA/Q, as defined by the standard deviation of the individual distribution functions, ranged from 0.12 to 0.19. One of the patients was characterized by a low mean VA/Q of 0.35, and the other patient had a wide dispersion (SD) of VA/Q of 0.37. In the normal subjects, a consistent VA/Q gradient was found only in the ventrodorsal direction. 133Xe and SPECT can be used to obtain meaningful biological information regarding ventilation/perfusion relationships of potential clinical value.

Adult↗

PubMed1999

NMDA-receptor activity visualized with (S)-[N-methyl-11C]ketamine and positron emission tomography in patients with medial temporal lobe epilepsy.

PURPOSE: To determine whether neurochemical activation of the N-methyl-D-aspartate (NMDA) receptor-gated ion channel shows quantitative changes, measured as binding of 11C-labeled (S)-[N-methyl]ketamine, in patients with medial temporal lobe epilepsy (MTLE). METHODS: Eight patients with MTLE who were evaluated regarding epilepsy surgery underwent positron emission tomography (PET) with (S)-[N-methyl-11C]ketamine. The presurgical investigations included magnetic resonance imaging (MRI), PET with 18F-fluoro-deoxyglucose (18FDG), and seizure monitoring by using video-EEG. The uptake of (S)-[N-methyl-11C]ketamine in the temporal lobe of ictal onset was compared with the contralateral side and correlated to changes in regional glucose metabolism measured by PET with 18FDG. RESULTS: (S)-[N-methyl-11C]ketamine rapidly reached the brain, and high radioactivities were measured in the striatum, thalamic nuclei, and cortical regions. Overall the brain uptake and regional binding potentials of (S)-[N-methyl-11C]ketamine were similar to measurements observed previously in healthy controls. However, 20 min after administration, when blood flow influence was negligible, a side-to-side comparison revealed a 9-34% reduction of tracer radioactivity in the temporal lobes of ictal onset. At earlier times, the differences in binding potentials were less pronounced, 9-21%. The magnitude and distribution of the reduction were similar to the metabolic pattern seen on PET scans with 18FDG. CONCLUSIONS: Radioactivity uptake of intravenously administered (S)-[N-methyl-11C]ketamine was reduced in temporal lobes of ictal in patients with TLE. This may reflect reduced NMDA-receptor density, reduced perfusion, focal atrophy, or other factors.

Adult↗

PubMed1999

Effect of normalization of hematocrit on brain circulation and metabolism in hemodialysis patients.

Full correction of anemia with recombinant human erythropoietin (rhEPO) has been reported to reduce the risk of cardiovascular morbidity and mortality and improve the quality of life in hemodialysis (HD) patients. Effects of normalization of hematocrit on cerebral blood flow and oxygen metabolism were investigated by positron emission tomography. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction ratio (rOER), and metabolic rate for oxygen (rCMRO2) were measured in seven HD patients before and after correction of anemia and compared with those in six healthy control subjects. In addition, blood rheology before and on rhEPO therapy was measured in HD patients, which included blood viscosity, plasma viscosity, erythrocyte fluidity, and erythrocyte aggregability. The results showed that plasma viscosity was high (1.51+/-0.19 mPa x s) and erythrocyte fluidity was low (85.8+/-4.8 Pa(-1) x s(-1)), while whole blood viscosity was within the normal range (3.72+/-0.38 mPa x s) before rhEPO therapy. After treatment, the hematocrit rose significantly from 29.3+/-3.3 to 42.4+/-2.2% (P<0.001), accompanied by a significant increase in the whole blood viscosity to 4.57+/-0.16 mPa x s, nonsignificant decrease in erythrocyte fluidity to 79.9+/-7.4 mPa(-1) x s(-1) and nonsignificant change in plasma viscosity (1.46+/-1.3 mPa x s). Positron emission tomography measurements revealed that by normalization of hematocrit, rCBF significantly decreased from 65+/-11 to 48+/-12 ml/min per 100 cm3 (P<0.05). However, arterial oxygen content (caO2) significantly increased from 5.7+/-0.7 to 8.0+/-0.4 mmol/L (P<0.0001), rOER of the hemispheres significantly increased from 44+/-3 to 51+/-6% (P<0.05) and became significantly higher than healthy control subjects (P<0.05). In addition, rCBV significantly increased from 3.5+/-0.5 to 4.6+/-0.6 ml/100 cc brain tissue. The results showed that oxygen supply to the brain tissue increased with normalization of hematocrit, but it was accompanied by increased oxygen extraction in the brain tissue. This may be assumed to be related to the decrease of erythrocyte velocity in the cerebral capillaries as a result of the decreased blood deformability and the increased plasma viscosity.

Aged↗

PubMed1999

Deposition and disposition of [11C]zanamivir following administration as an intranasal spray. Evaluation with positron emission tomography.

OBJECTIVE: This study used positron emission tomography (PET) to investigate the deposition and disposition of zanamivir administered as a nasal spray. DESIGN: This was an open-label single-dose study in healthy volunteers. STUDY PARTICIPANTS: Six healthy male volunteers, aged 19 to 33 years (mean age 25 years) with a bodyweight of 65 to 94 kg (mean bodyweight 76 kg), took part in the study. INTERVENTIONS: Each participant received by nasal spray zanamivir 6.4 mg mixed with, on average, 2.5 MBq of [11C]zanamivir. The amount of radioactivity was recorded sequentially in 5 different sectors of the body, starting with a short dynamic sequence over the nasal passage. Each of the regions was examined 1 to 4 times at different times after inhalation. The duration of the examination was 90 minutes. During this time, multiple blood samples were taken for analysis of radioactivity in whole blood. Serum samples for pharmacokinetic determinations were collected for 8 hours after administration. RESULTS: Immediately after administration, about 90% of the drug was deposited in the nasal passage, decreasing to 48% at 90 minutes after administration. Less than 2% was detected in the lower respiratory tract. The major elimination route was via the oesophagus to the stomach. Approximately 2% of the dose was absorbed; the median maximum drug concentration in serum was 15 micrograms/L, and occurred around 1.75 hours after inhalation. CONCLUSIONS: The major deposition site for zanamivir administered by nasal inhalation is the nasal passage; half of the drug remains there for at least 1.5 hours after administration. PET seems to be an excellent tool for this type of kinetic study, allowing imaging and measurements of inhaled drugs with high quantitative accuracy and good spacial resolution.

Administration, Intranasal↗