Spelling suggestions: "subject:"pharmacokinetics"" "subject:"harmacokinetics""
521 |
The effect of oral lipids and lipoproteins on the biodistribution, metabolism and electrocardiographic side-effects of halofantrinePatel, Jigar Unknown Date
No description available.
|
522 |
The effects of hyperlipidemia on the pharmacokinetic and pharmacodynamic aspects of amiodarone and ketoconazoleEl Sayed, Dalia Unknown Date
No description available.
|
523 |
The effects of iron deficiency on the efficacy and pharmacokinetics of albendazole in mice infected with Heligmosomoides polygyrus /Nielsen, Kim January 1994 (has links)
The aim of this research was to determine the influence of iron deficiency on both the efficacy and metabolic patterns of albendazole in mice infected with Heligmosomoides polygyrus. Anthelmintic efficacy was markedly decreased in iron-deficient mice; the deficiency was also associated with a decrease in body weight, altered hematological parameters and a decreased net egg output; worm establishment in the deficient group was not affected by the deficiency. Although anthelmintic efficacy was significantly decreased by the iron deficiency, plasma concentration profiles of the main metabolites, albendazole sulphoxide and albendazole sulphone, were not changed by the deficiency. Levels of intestinal cytochrome P-450, the main metabolizing enzyme of albendazole however, was significantly depressed in iron-deficient mice. These observations suggest that although pharmacokinetic parameters are not affected by iron deficiency, nutritional status has the potential to influence anthelmintic efficacy and thus warrants further study.
|
524 |
Pharmacokinetic modeling of pollutant fluxes by limnoplanktonWen, Yuan Hua. January 1996 (has links)
The objective of this thesis was to construct general models to predict pollutant fluxes in limnoplankton by incorporating characteristics of the organism and the structures of the chemical. A two-compartmental pharmacokinetic model was used to quantify the pollutant uptake, depuration and intercompartmental exchanges. The model pollutants were phosphorus and 22 organic chemicals. / The rate constants of phosphorus uptake, excretion and intercompartmental changes by algae and cladocerans decreased with cell volume or body size raised to a power close to $-$0.25, except the intercompartmental exchanges for cladocerans which showed more negative slopes. In contrast, uptake, excretion and internal exchange rates per individual increased with cell size or body weight to a power similar to 0.75 with a similar exception for the cladoceran intercompartmental exchanges, which had slopes $<$0.75. / Bioconcentration factors, rate constants and flux rates of uptake and intercompartmental exchange from metabolic pool to structural pool of 22 $ sp{14}$C-labelled organic toxicants by Chlorella pyrenoidosa and Daphnia magna were positively correlated with the octanol/water partition coefficient, molecular weight, parachor, connectivity index, boiling point and melting point, and negatively with aqueous solubility. However, those of elimination and internal transfer from structural pool to metabolic pool showed opposite changes. Comparisons of pharmacokinetic parameters between Daphnia and Chlorella demonstrated that, although all kinetic parameters displayed similar patterns, the relative magnitudes of each corresponding parameters were significantly different between two species.
|
525 |
Studies on some pharmacological properties of Capsicum frutescens-driven capsaicin in experimental animal models.Jolayemi, Adebayo Taiwo Ezekiel. January 2012 (has links)
The present study investigated pharmacological properties of Capsicum frutescens-derived capsaicin, including its analgesic, anti-inflammatory and coagulatory properties. The effects of capsaicin on gastrointestinal and myocardial muscles, as well as on myocardial ischaemic-reperfusion, were also investigated.
Capsaicin pre-treatment in neonatal rats has been found to abolish the development of thermal hyperalgesia produced in a model of neuropathic pain in rats (Toth-Kasa et al., 1986). In addition, capsaicin sensitivity has been found to be dependent on continued presence of nerve growth factor (NGF), whose concentration increases in inflamed tissues (Bevan and Winter, 1995). By stimulating the release of excitatory amino acids (EAA); such as glutamate and neuropeptides [(CGRP, neurokinin A (NKA) and Substance P (SP)] from both the peripheral and central terminals of sensory neurones by two mechanisms (Kroll et al., 1990; Del Bianco et al., 1991; Lou et al., 1992; 1994; Woolf et al., 1994); capsaicin has been shown to produce a longer-term inhibitory effect. This is one likely mechanism for capsaicin analgesic and anti-inflammatory actions (Bleakman et al., 1990).
Within the gastro-intestinal tract, SP and NKA are involved in the physiological control of several digestive functions, such as motility, fluid and electrolyte secretion, blood flow, and tissue homeostasis (Otsuka, 1993; Holzer et al., 1997). Consistent with this finding, upsurge of SP in irritable bowel syndrome (IBD) was confirmed by Mantyh et al, (1988). Pre-treatment of rats with either capsaicin or NK-1R antagonists dramatically reduced fluid secretion, mucosal permeability, and intestinal inflammation in animal models of acute and chronic inflammation (McCafferty et al, 1994; Pothoulakis et al., 1994).
Capsaicin can modulate endocrine and paracrine activities, immune responses, as well as gastro-intestinal and cardiovascular functions. Moreover, up-regulation of Substance P receptors was found to be associated with chronic inflammatory conditions (De et al., 1990). Stimulation of transient receptor potential vanilloid 1 also results in the activation of nociceptive and neurogenic inflammatory responses (Rigoni et al., 2003).
vi
The pharmacodynamic effects of capsaicin on the cardiovascular system remain elusive. Some actions of capsaicin on the heart were attributed to an interaction at K+ channels (Castle, 1992), or liberation of neuropeptides, most notably calcitonin-gene-related-peptide (CGRP) from the vanilloid-sensitive innervation of the heart (Franco-Cereceda et al., 1988; 1991). The possibility of a direct effect of capsaicin on the heart via a cardiac vanilloid receptor (VR), or through interaction of vanilloid receptors with purinergic receptors, and subsequent release of nitric oxide (NO), leading to vasodilatation were considered. Evidence abound in the literature that Ca2+ ions are released through 1, 4, 5 inositol phosphatase by the release of phospholipase C, or through interaction of the vanilloid receptors with cannabinoids. In an earlier study, Jaiarj et al. (1998) found that capsaicin acting on the heat-sensitive vanilloid receptors, had thrombolytic effects. Though weak evidence, Jaiarj et al. (1998) observed that individuals who consume large amounts of Capsicum have lower incidence of thromboembolism.
Following ethical approval, the study reported in this thesis was conducted in phases. Identification of Capsicum frutescens (facilitated by a botanist in the Department of Botany, Westville campus of the University of KwaZulu Natal). Chromatographic extraction of capsaicin from Capsicum frutescens was followed by Nuclear Magnetic Resonance (NMR) analysis of the extract. Animal studies were conducted using capsaicin extract (CFE) and/or a reference capsaicin (CPF), using „hot plate. and „acetic acid. test methods to investigate the role of capsaicin on analgesia. Fresh egg albumin-induced inflammation was used to investigate the role of capsaicin in inflammation, following pre-treatment with CFE and CPF. Concentraton-response curves of increasing concentrations of capsaicin, acetylcholine and other agonist drugs with specific antagonists on strips of chick oesophagus, guinea-pig ileum, and rabbit duodenum were constructed following investigations on gastrointestinal (GIT) smooth muscles. The effect of capsaicin on coagulation was assessed by measuring international normalized ratio (INR) of animals that were exposed to different concentrations of capsaicin (CFE and CPF). Furthermore, parallel control studies were conducted in each of these investigations using distilled water or saline as placebo-control or specific-prototype agonists. negative-control. Cardiovascular investigations included studies on the effects of capsaicin on the heart rate, inotropy,
vii
coronary perfusion pressure, and ischaemic-reperfusion injury, using Langendorf.s rat heart models.
Collated data were triangulated by manual hand-written and PowerLab data acquisition, or computerised capture. Statistical analysis were performed by either one or two of the following: Student.s t-test, ANOVA (repeated or single–use modes), facilitated and confirmed by Graph Pad Prism, Microsoft Excel or CPSS software(s).
Reproducibility and relevance to the stated objectives of the various studies were confirmed by assessing which of the Null or Alternative hypothesis is validated by the results from the test.
Treatment with CFE or CPF at all doses significantly (p<0.01) increased MRT. By comparison with control, writhing responses to acetic acid were significantly reduced following pre-treatment with various doses of CFE or CPF. The results in both parallel groups of CFE and CPF in the hot plate and acetic acid tests had Pearson correlation of one (1).
Compared to the diclofenac (DIC) group, the degree of inhibition of paw oedema by CFE and CPF was statistically significant (P<0.05-0.001), best in the first 4 hours of treatment.
The results of the in vitro laboratory animal study indicate that relatively low concentration of CPF (20 or 40 .g) produced significant (p.0.05), concentration-related inhibitions of acetylcholine (0.1-5 .g)-induced contractions of the chick isolated oesophagus, guinea-pig isolated ileum and rabbit isolated duodenum. Biphasic effects, which were noticed at low concentrations, consisted of initial brief contractions, followed by longer-lasting relaxations and reductions of the contractile amplitudes of the muscle preparations. Percentage inhibitions of the smooth muscle contractions by CFE or CPF were concentration-dependent, ranging from 20-70% (p<0.02). / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2012.
|
526 |
The pharmacokinetics/pharmacodynamics of theophylline in premature neonates during the first few days after birth.Du Preez, Marie J. January 2000 (has links)
Theophylline is one of the few preparations available for the treatment of apnoea of
prematurity. Currently little data is available on the pharmacokinetics and the
pharmacokinetic/pharmacodynamic relationships of theophylline for premature neonates
during the first few days of life, a time when neonates undergo profound physiological
changes and when the drug is most often used. Furthermore, the influence of
theophylline on hypoxaemic episodes has not yet been quantified.
The study aimed to investigate optimal theophylline dosing in this group by establishing
pharmacokinetic parameters, assessing the effectiveness of the drug in abolishing apnoea
and hypoxaemic episodes and investigating the concentration/effect relationship.
The project was conducted in the neonatal wards of King Edward VIII Hospital, Durban,
South Africa. The study group comprised a total of 105 Black, apnoeic, premature
neonates, with respiratory distress syndrome, who were receiving intravenous
theophylline. Serum samples (263), collected from patients during routine care, were
analysed for theophylline. Forty-six patients were monitored before and after
theophylline therapy with a neonatal capnograph linked to a data acquisition.
Apnoea incidents were classified into total (all apnoea <_5 seconds) and pathologic (all apnoea >_20 seconds) and a hypoxaemic episode was defined as a >_10% fall for >10
seconds in peripheral oxygen saturation. Within each of these groups patients were assessed as responders (>_50% reduction in the clinical effect from baseline to the last
recording) and non-responders. Patient characteristics were identified as possible
markers of non-response to theophylline therapy.
The Nonlinear Mixed Effects Model (NONMEM) was used to derive population
pharmacokinetic models and parameters for theophylline as well as to assess the
concentration-effect relationship.
The pharmacokinetic analysis estimated a low clearance and volume of distribution, with
oxygen support enhancing clearance. Relatively high inter-individual and residual
variability values were obtained prompting testing for inter-occasion variability. This
resulted in a decrease of inter-individual variability for clearance and volume of
distribution as well as in residual variability.
In the theophylline doses used, a significant reduction in total and pathologic apnoea but
not in hypoxaemic episodes occurred over the first three days after birth. The most
positive improvement was seen on the first day of treatment after the loading dose. A
statistically significant increase in the average pulse rate and a decrease in episodes of
bradycardia from baseline to all three days of monitoring were recorded.
Most patients responded at serum theophylline concentrations of 3 to 9 mg/L. Most serum theophylline concentration measurements were also in this range and it was not
possible to clearly define a concentration-effect relationship. The cumulative percentage
of non-responders was relatively high for total apnoea (48%) and hypoxaemic episodes
(45%), but low for pathological apnoea (13%). Being one of a set of twins was identified
as a marker of poor response for both total apnoea and hypoxaemic episodes. Other
possible markers for poor response, in terms of total hypoxaemic episodes, were being
born by caesarean section and having more than the 75th percentile pathologic apnoea per
hour at baseline. It was interesting to note that, with regard to total apnoea, there were
some features that seemed to predict a favourable response to theophylline. These were
birth weight and 5 minute Apgar score below the 25th percentile, and patients with
baseline total apnoea counts above the 75th percentile.
The cumulative graphs of the responders and non-responders resembled the fixed effect
model, which is the simplest model to explain drug-effect relationships. More
sophisticated analysis of the concentration-effect relationship, using NONMEM and the
count model proved difficult. None of the models tested were found to be satisfactory,
but that which included the influence of a hypothetical respiratory depressant factor gave the most realistic value of EC50. It is suggested that further even more complex
modelling may be required to accurately define the concentration-effect relationship (and
hence the therapeutic range) for theophylline in neonatal apnoea. / Thesis (Ph.D.)-University of Natal, Durban, 2000.
|
527 |
Effects of Acute Aerobic Exercise on the Pharmacokinetics of the Anti-anxiety/Anti-depressant Drug SertralineRuderman, Ethan B. W. 10 December 2013 (has links)
This study examined the effects of 30 minutes of cycle exercise at 65% V̇O2max on the pharmacokinetics of the S.S.R.I. sertraline. Blood samples were taken over 48 hours from 14 healthy males (23.9±2.5 years, 80.3±12.6 kilograms) following oral ingestion of a single 100 mg dose of sertraline. Participants completed two sertraline trials separated by at least two weeks; one trial while resting and the other trial with exercise as described above. With exercise, the absorption rate constant and volume of sertraline in the central compartment decreased, while the elimination half-life increased. Maximum concentration, time of maximum concentration, and area under the curve were unchanged. Fitness level had little impact on the concentration of sertraline, as compartmental modeling was unchanged when relative V̇O2max was added as a covariate. However, controlling for participant body weight improved the model estimate. These results indicate that acute aerobic exercise has the potential to change the concentration of sertraline in vivo.
|
528 |
Model-Based Therapeutics for Type 1 Diabetes MellitusWong, Xing-Wei January 2008 (has links)
The incidence of Type 1 diabetes is growing yearly. Worryingly, the aetiology of the disease is inconclusive. What is known is that the total number of affected individuals, as well as the severity and number of associated complications are growing for this chronic disease. With increasing complications due to severity, length of exposure, and poor control, the disease is beginning to consume an increasingly major portion of healthcare costs to the extent that it poses major economic risks in several nations. Research has shown that intensive insulin therapy aimed at certain minimum glycosylated haemoglobin threshold levels reduces the incidence of complications by up to 76% compared to conventional insulin therapy. Moreover, the effects of such intensive therapy regimes over a 6.5y duration persists for at least 10y after, a so called metabolic memory. Thus, early intervention can slow the momentum of complications far more easily than later intervention. Early, safe, intensive therapy protocols offer potential solutions to the growing social and economic effects of diabetes. Since the 1970s, the artificial endocrine pancreas has been heralded as just this type of solution. However, no commercial product currently exists, and ongoing limitations in sensors and pumps have resulted in, at best, modest clinical advantages over conventional methods of insulin administration or multiple daily injection. With high upfront costs, high costs of consumables, significant complexity, and the extensive infrastructure and support required, these systems and devices are only used by 2-15% of individuals with Type 1 diabetes. Clearly, there is an urgent need to address the large majority of the Type 1 diabetes population using conventional glucose measurement and insulin administration. For these individuals, current conventional or intensive therapies are failing to deliver recommended levels of glycaemic control. This research develops an understanding of clinical glycaemic control using conventional insulin administration and glucose measurement techniques in Type 1 diabetes based on a clinically validated in silico virtual patient simulation. Based on this understanding, a control protocol for Type 1 diabetes that is relatively simple and clinically practical is developed. The protocol design incorporates physiological modelling and engineering techniques to adapt to individual patient clinical requirements. By doing so, it produces accurate, patient-specific recommendations for insulin interventions. Initially, a simple, physiological compartmental model for the pharmacokinetics of subcutaneously injected insulin is developed. While the absorption process itself is subject to significant potential variability, such models enable a real-time estimation of plasma insulin concentration. This information would otherwise be lacking in the clinical environment of outpatient Type 1 diabetes treatment due to the inconvenience, cost, and laboratory turnaround for plasma insulin measurements. Hence, this validated model offers significant opportunity to optimise therapy selection. An in silico virtual patient simulation tool is also developed. A virtual patient cohort is developed on patient data from a representative cohort of the broad diabetes population. The simulation tool is used to develop a robust, adaptive protocol for prandial insulin dosing against a conventional intensive insulin therapy, as well as a controls group representative of the general diabetes population. The effect on glycaemic control of suboptimal and optimal, prandial and basal insulin therapies is also investigated, with results matching clinical expectations. To gauge the robustness of the developed adaptive protocol, a Monte Carlo analysis is performed, incorporating realistic and physiological errors and variability. Due to the relatively infrequent glucose measurement in outpatient Type 1 diabetes, a method for identifying the diurnal cycle in effective insulin sensitivity and modelling it in retrospective patient data is also presented. The method consists of identifying deterministic and stochastic components in the patient effective insulin sensitivity profile. Circadian rhythmicity and sleep-wake phases have profound effects on effective insulin sensitivity. Identification and prediction of this rhythm is of utmost clinical relevance, with the potential for safer and more effective glycaemic control, with less frequent measurement. It is thus a means of further enhancing any robust protocol and making it more clinically practical to implement. Finally, this research presents an entire framework for the realistic, and rapid development and testing of clinical glycaemic control protocols for outpatient Type 1 diabetes. The models and methods developed within this framework allow rapid and physiological identification of time-variant, patient-specific, effective insulin sensitivity profiles. These profiles form the responses of the virtual patient and can be used to develop and robustly test clinical glycaemic control protocols in a broad range of patients. These effective insulin sensitivity profiles are also rich in dynamics, specifically those circadian in nature which can be identified, and used to provide more accurate glycaemic prediction with the potential for safer and more effective control.
|
529 |
The in vitro and in vivo pharmacokinetic parameters of polylactic-co-glycolic acid nanoparticles encapsulating anti-tuberculosis drugs / L.L.I.J. BooysenBooysen, Laetitia Lucretia Ismarelda Josephine January 2012 (has links)
Tuberculosis (TB) is an infectious, deadly disease, caused by Mycobacterium tuberculosis
(M.tb). In 2010, there were 8,8 million incident cases of TB globally. South Africa currently
has the third highest TB incident cases worldwide. In an attempt to address the challenges
facing TB chemotherapy, among which frequent dosing and long duration of therapy resulting
in poor patient compliance, a novel poly(DL-lactic-co-glycolic) acid (PLGA) nanoparticulate
drug delivery system (DDS) encapsulating anti-TB drugs was developed. It is hypothesised
that this nanoparticulate DDS will address the challenges mentioned by enabling decreased
dosing frequency, shortening duration of therapy and minimising adverse side effects.
Therefore, favourable modification of pharmacodynamic (PD) and pharmacokinetic (PK)
properties of the conventional anti-TB drugs was demonstrated. Furthermore, the
nanoparticles will provide a platform for drug delivery to macrophages that serve as hosts for
M.tb.
The study design was based on determining specific physicochemical properties of the
nanoparticulate DDS to elucidate the hypothesis. Spray-dried PLGA nanoparticles were
prepared using the double emulsion solvent evaporation technique. In vivo analysis of
macrophage uptake and possible immunological response in mice were evaluated. In vitro
protein-binding assays of PLGA nanoparticles encapsulating anti-TB drugs isoniazid (INH)
and rifampicin (RIF) were performed with subsequent in vivo tissue distribution assays to
support protein-binding data generated. Finally, PK/PD analyses were conducted to evaluate
the effect of nanoencapsulation on the anti-TB drugs. These involved in vitro assays to
determine if sufficient drug was released from the nanoparticles to exhibit minimum inhibitory
concentration (MIC) and minimum bactericidal concentrations (MBC). Furthermore, in vivo
drug distribution and drug release kinetics assays of encapsulated RIF, INH, pyrazinamide
(PZA) and ethambutol (ETB) in a mouse model were performed.
The results confirmed that the PLGA nanoparticles (<250 nm, low positive zeta potential)
were taken up by macrophages in vivo with no significant immunological effect. Furthermore
the nanoparticles were present in the brain, heart, kidneys, lungs, liver and spleen for up to 7
days following once-off oral dosing at 13.23± 0.11%, 16.81± 0.11%, 54.89± 0.95%, 15.61±
1.15%, 48.48± 2.28% and 5.73± 0.21%, respectively. This was further confirmed by drug
analysis demonstrating the presence of INH, RIF and ETB at different time points up to 7 days in the lungs, kidneys, liver and spleen. However, PZA was not detected. Nanoencapsulated
RIF and INH exhibited MICs and MBCs in vitro over 14 days and these drugs were also
observed in plasma for up to 7 days post once-off oral dosing. ETB and PZA were observed
up to 3 days.
From the results generated, it can be concluded that the nanoparticles were taken up by
macrophages without eliciting an immune response. This provides a platform for drug delivery
to specific sites. Furthermore, the nanoparticulate DDS exhibited sustained drug release
in vitro and in vivo over a number of days above the MIC for the drugs analysed. Sustained
drug distribution was also observed. It can therefore be concluded that the hypothesised
reduction in dose frequency and duration of therapy for this DDS is a possibility / Thesis (PhD (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013
|
530 |
The in vitro and in vivo pharmacokinetic parameters of polylactic-co-glycolic acid nanoparticles encapsulating anti-tuberculosis drugs / L.L.I.J. BooysenBooysen, Laetitia Lucretia Ismarelda Josephine January 2012 (has links)
Tuberculosis (TB) is an infectious, deadly disease, caused by Mycobacterium tuberculosis
(M.tb). In 2010, there were 8,8 million incident cases of TB globally. South Africa currently
has the third highest TB incident cases worldwide. In an attempt to address the challenges
facing TB chemotherapy, among which frequent dosing and long duration of therapy resulting
in poor patient compliance, a novel poly(DL-lactic-co-glycolic) acid (PLGA) nanoparticulate
drug delivery system (DDS) encapsulating anti-TB drugs was developed. It is hypothesised
that this nanoparticulate DDS will address the challenges mentioned by enabling decreased
dosing frequency, shortening duration of therapy and minimising adverse side effects.
Therefore, favourable modification of pharmacodynamic (PD) and pharmacokinetic (PK)
properties of the conventional anti-TB drugs was demonstrated. Furthermore, the
nanoparticles will provide a platform for drug delivery to macrophages that serve as hosts for
M.tb.
The study design was based on determining specific physicochemical properties of the
nanoparticulate DDS to elucidate the hypothesis. Spray-dried PLGA nanoparticles were
prepared using the double emulsion solvent evaporation technique. In vivo analysis of
macrophage uptake and possible immunological response in mice were evaluated. In vitro
protein-binding assays of PLGA nanoparticles encapsulating anti-TB drugs isoniazid (INH)
and rifampicin (RIF) were performed with subsequent in vivo tissue distribution assays to
support protein-binding data generated. Finally, PK/PD analyses were conducted to evaluate
the effect of nanoencapsulation on the anti-TB drugs. These involved in vitro assays to
determine if sufficient drug was released from the nanoparticles to exhibit minimum inhibitory
concentration (MIC) and minimum bactericidal concentrations (MBC). Furthermore, in vivo
drug distribution and drug release kinetics assays of encapsulated RIF, INH, pyrazinamide
(PZA) and ethambutol (ETB) in a mouse model were performed.
The results confirmed that the PLGA nanoparticles (<250 nm, low positive zeta potential)
were taken up by macrophages in vivo with no significant immunological effect. Furthermore
the nanoparticles were present in the brain, heart, kidneys, lungs, liver and spleen for up to 7
days following once-off oral dosing at 13.23± 0.11%, 16.81± 0.11%, 54.89± 0.95%, 15.61±
1.15%, 48.48± 2.28% and 5.73± 0.21%, respectively. This was further confirmed by drug
analysis demonstrating the presence of INH, RIF and ETB at different time points up to 7 days in the lungs, kidneys, liver and spleen. However, PZA was not detected. Nanoencapsulated
RIF and INH exhibited MICs and MBCs in vitro over 14 days and these drugs were also
observed in plasma for up to 7 days post once-off oral dosing. ETB and PZA were observed
up to 3 days.
From the results generated, it can be concluded that the nanoparticles were taken up by
macrophages without eliciting an immune response. This provides a platform for drug delivery
to specific sites. Furthermore, the nanoparticulate DDS exhibited sustained drug release
in vitro and in vivo over a number of days above the MIC for the drugs analysed. Sustained
drug distribution was also observed. It can therefore be concluded that the hypothesised
reduction in dose frequency and duration of therapy for this DDS is a possibility / Thesis (PhD (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013
|
Page generated in 0.0849 seconds