Biomedical subjects

T Trnovec

Publications and source records attributed to T Trnovec.

At least 19 recordsLinked to original sources

PubMed2000

Direct high-performance liquid chromatographic determination of (R)- and (S)-propranolol in rat microdialysate using on-line column switching procedures.

Two different column-switching HPLC systems (CSWs), employing restricted access material for initial pretreatment of biological samples, were developed for the determination of propranolol enantiomers in microdialysate. CSW 1 was a single-pump set-up based on an initial sample clean-up step with a RP-18 ADS precolumn coupled with an ovomucoid analytical column for direct drug enantioseparation. For the two-pump column set-up (CSW 2), a teicoplanin analytical column was applied for the enantioselective assay after initial sample pretreatment using a RP-8 ADS precolumn. The inter-day precision of the CSW 1 ranged from 0.5 to 5.1% for (R)-propranolol and from 5.1 to 10.5% for (S)-propranolol. The limit of detection (LOD) was set at 10 ng/ml and 15 ng/ml for (R)- and (S)-propranolol, respectively. Inter-day relative standard deviation values of the CSW 2 ranged from 1.1 to 9.9% for (R)-propranolol and from 1.3 to 9.6% for (S)-propranolol. The LOD of the method was 3.0 ng/ml for (R)-propranolol and 2.5 ng/ml for (S)-propranolol. Both approaches were successfully applied for stereoselective monitoring of unbound propranolol levels in rat microdialysates.

Adrenergic beta-Antagonists↗

PubMed2000

[The prehospital phase in patients with acute myocardial infarct in Slovakia. A challenge].

Better management of patients with acute myocardial infarction during the prehospital phase is at present a challenge not only for health workers but for society as a whole. The authors pay attention to knowledge of the complex problem of the prehospital phase in patients with acute myocardial infarction which is a prerequisite for finding possible solutions for a favourable effect on their management. The authors analyzed 3,040 patients who were admitted to hospital alive within 96 hours after the development of complaints with suspicion of a first or repeated acute myocardial infarction. They focused attention in particular on prehospital time delay. They found that within a satisfactory time interval (within 2 hours) 29.8% patients were delivered and within a yet acceptable interval of 4 hours 51.6% patients (with respect to effectiveness of thrombolytic treatment). Similarly undesirable are also data on the patient time delay. Within the optimal first hour after development of complaints following the decision of the patient (subjects present) to ask for or seek medical assistance was the decision of 34% patients, during the first two hours 47.5% and within 4 hours 61.2% patients with acute myocardial infarction. The ratio of time delay of the patient in the total prehospital delay is 45.5% even in patients who were admitted during the first hour after development of acute myocardial infarction. In patients who were admitted 4 hours after development of complaints it is 79.5%. The patient is admitted to hospital most quickly if he calls the medical emergency service and latest when he decides to see a doctor. Physicians and other health workers contributed only in 16.4-20.9% patients with acute myocardial infarction to their early decision to seek medical assistance. Patients with an early decision (within one hour) call most frequently the medical emergency service and are taken to hospital by this service. The time delay due to transport is shortest in these patients. The late hospital admission of patients with acute myocardial infarction in Slovakia calls for reduction of the time interval from the development of complaints to hospital admission (total prehospital delay), in particular the time taken by the patient to make up his mind (patient time delay). Early calling of the emergency medical service and transport of the maximum possible number of patients with acute myocardial infarction to hospital by the emergency medical service will greatly improve the management of patients with acute myocardial infarction. Comprehensive implementation of the survival chain (24), the most comprehensive implementation of recommendations of the European Society of Cardiology and the European Resuscitation Council for in the management of patients with acute heart attacks during the prehospital phase (21) and early effective treatment which begins already in the prehospital phase has a favourable impact on the condition of patients with acute myocardial infarction and on their prognosis. Along with early and effective treatment of patients with acute myocardial infarction in hospital and their stratification these are the most important approaches to the development and control of sudden cardiac death. Knowledge of the complex problem of the prehospital phase in patients with acute myocardial infarction is the prerequisite for the elaboration of high standard prehospital management of patients with acute myocardial infarction.

Adult↗

PubMed1999

Pharmacokinetic study of stobadine.

The aim of this paper is to provide a brief overview of most important results of stobadine kinetic studies in rats, dogs, and human volunteers. In these studies, stobadine dihydrochloride and stobadine dipalmitate was used for intravenous and oral administration, respectively. To evaluate kinetic properties of stobadine and its metabolites, TLC, HPLC, GLC, GC-MS, radiometric, and fluorometric methods were developed and used.

Animals↗

PubMed1999

[Pharmacotherapeutic profile of patients with acute myocardial infarct in the early hospitalization period].

BACKGROUND: The early treatment efficacy of patients with acute myocardial infarction (AMI) with thrombolysis, antiplatelet drugs, betablockers and ACE inhibitors has been well documented in randomized mega trials. However, little is known about the fact to what extend the results of these mega trials have influenced the treatment practices. Moreover, in the view of a complete lack of data on management of patients with AMI in Slovak Republic a project of the Ministry of Health "Audit of diagnostic and therapeutic management in patients with acute coronary syndromes" (AUDIT) has been conducted. OBJECTIVES: To obtain preliminary information on the present state of pharmacotherapy of patients with AMI in Slovak Republic during the early hospitalization phase (EHP) from the Pilot Study (PS) of the project AUDIT. METHODS: Pharmacotherapy of AMI during EHP was analysed in 336 patients (232 males and 104 females, mean age 65 12 years, age range 30-93 years). Patients admitted with diagnosis of the first or repeated AMI or with suspect AMI were included. PS was done in prospective multicentric study between November 1, 1996 and December 31, 1996. 23 hospitals from various parts of Slovakia participated in this study. Data were compiled by means of questionaires and were processed by ACCES 97 and EXCEL 97. RESULTS: Antiplatelet therapy with acetylosalicylic acid (almost exclusively Anopyrin) received as much as 87.8% of patients with AMI during EHP. Thrombolytic therapy (TLT), almost exclusively with streptokinase, was performed in 105, i.e. in 31.8% of patients with AMI. TLT was performed in a statistically significantly smaller proportion of patients older than 65 years compared to patients 65 years of age and younger (20.9% vs 41.2%, p < or = 0.01). Females were treated with TLT statistically significantly less frequently than males (24.5% vs 35.1%, p < or = 0.05). The major cause for not performing the TLT was late arrival to hospital (in 32.1% patients). Betablockers were administered to a total of 42.9% of patients during EHP. Betablockers received only 3.6% of patients intravenously (!) and only 39.3% of patients orally. Treatment with oral betablockers was performed in a statistically significantly smaller proportion of patients older than 65 years compared to patients 65 years of age and younger (27.4% vs 49.7%, p < or = 0.01). Up to 49.1% of patients in EHP were treated with ACE inhibitors, however, left ventricular ejection fraction < 40% warranting feasibility of this treatment was achieved only in 26.7% of patients. Nitrates were administered to 62% of patients in EHP, of this number intravenously to 37.4% of patients. Calcium channel blockers were given only to 7.3% of patients. Treatment with heparin was performed in 90.9% of patients. 14.3% of patients received during EHP antiarrhythmics of class I and 2.7% of patients of class III. MgSO4 was used in 26.4% of patients in EHP. CONCLUSIONS: The reported PS of AUDIT Project gives for the first time information on the state of the pharmacotherapy of patients with AMI in Slovak Republic. Some results are relatively encouraging, however, others can not be a reason for satisfaction. The fact, that in Slovakia, adequate number of patients with AMI receive acetylosalicylic acid (Anopyrin) and that Slovakia belongs to countries with the smallest proportion of patients with AMI treated with calcium channel blockers and antiarrhythmics during EHP is encouraging. On the other hand, the use of TLT and betablockers is dissatisfactory. Requirement to increase the proportion of thrombolysed patients with AMI and the necessity for substantially more frequent use of betablockers, especially intravenous, in EHP in these patients result from these findings. In Slovakia, inadequately large proportion of patients with AMI is treated with ACE inhibitors, heparin, and partially also nitrates administered per os during EHP. (ABSTRACT TRUNCATED)

Adrenergic beta-Antagonists↗

PubMed1998

[In Process Citation]

Project Audit of diagnostic and therapeutic procedures in patients with acute coronary syndromes was approved by the Ministry of Health of the Slovak Republic on 13 May 1996. The essence of the project resides in a systematic and complex analysis of quality of provided medical care and the use of sources with the seeking for possibilities of improvement of the provided care aimed at prognosis and quality of life of patients with acute coronary syndrome (acute infarction, unstable angina pectoris, sudden cardiac death). The subsequent step will reside in the Project of Sudden Cardiac Death Prevention and the establishment of the myocardial infarction register.

Journal Article↗

PubMed1998

Informacia o niektorych vysledkoch z Pilotnej studie projektu Ministerstva zdravotnictva SR. AUDIT diagnostickeho a terapeutickeho postupu u chorych s akutnymi koronarnymi syndromami

The basic analysis of the Pilot study fully confirms the possibilities of the realization of the project AUDIT ... in the planned form, the necessity to realize this project regarding the discovery of several negative facts in the management of patients with AMI, which can affect infavourable the course of the disease in patients with AMI and their prognosis or unjustifiably increase the economic impact. The most severe of them are investigated in this information and we present them in subsequent order of individual phases of the management of patients afflicted by AMI.

Journal Article↗

PubMed1997

Effects of blockade of Kupffer cells by gadolinium chloride on hepatobiliary function in cold ischemia-reperfusion injury of rat liver.

The mechanisms of liver injury from cold storage and reperfusion are not completely understood. The aim of the present study was to investigate: 1) whether the inactivation of Kupffer cells (KCs) by gadolinium chloride (GadCl) modulates cold ischemia-reperfusion injury of rat liver; and 2) whether cold storage of rat liver involves injury to biliary epithelial cells (BECs). Hepatobiliary function was assessed using an isolated perfused rat liver model. Compared with control livers, in livers subjected to cold storage at 4 degrees C in Euro-Collins solution (EC) for 18 hours or in University of Wisconsin solution (UW) for 48 hours, portal flow was lower and resistance significantly higher, taurocholate (TC) and bromosulfophthalein (BSP) elimination were markedly impaired, bile flow was reduced, and lactate dehydrogenase (LDH) leakage into the perfusate was increased. Pretreatment of rats with GadCl, a selective KC toxicant, abrogated disturbances of the microcirculation in both models, but it did not influence viability and functional parameters of the liver. Most of the parameters studied in livers stored in UW solution for 18 hours were not significantly different from those found in control livers. As to biliary activity of gamma-glutamyl transferase (GGT), as an index of BEC integrity, it was increased with increasing time of cold storage. The reabsorption of glucose from the bile decreased with longer storage time. The results suggest the following: 1) that cold ischemia-reperfusion injury of rat liver is mediated by KC-dependent (hepatic microcirculation) and -independent (parenchymal cell function) mechanisms; and 2) that cold storage of rat liver induces functional impairment of BECs.

Animals↗

PubMed1997

Relationship between plasma fenofibric acid levels and the effect of micronized fenofibrate on cholesterol, low-density-lipoprotein cholesterol and apolipoprotein B in patients with primary hypercholesterolemia.

OBJECTIVE: We examined the relationship between plasma levels of fenofibric acid, the active metabolite of fenofibrate, and differences in concentrations of plasma lipids, in subjects with primary type IIA or IIB hyperlipoproteinemia (HLP). SUBJECTS AND METHODS: Twenty-nine patients (13 with type IIA and 16 with type IIB HLP) were treated with a single daily 200-mg dose of micronized fenofibrate for 3 months, after which the plasma levels of fenofibric acid were determined by HPLC after an overnight fast. RESULTS: In the type IIA HLP phenotype, statistically significant correlations were found between fenofibric acid levels and changes in total cholesterol, LDL-C and apo-B at all three control visits, with the highest correlation coefficients at V3 visit (total cholesterol r = 0.85. LDL-C r = 0.68, apo-B r = 0.85). In type IIB HLP, statistical significance was confirmed only when performing an analysis of pooled values for total cholesterol and LDL-C (r = 0.42, r = 0.34, respectively). The high correlation between plasma fenofibric acid levels and its effect on beta lipoprotein changes might reflect the effect of fenofibrate on the catabolism of plasma LDL by the LDL receptor, since that type of relationship is typical of drugs which directly influence the target compartment without an effect on intermediary steps of metabolism. An explanation for the different levels of correlations in type IIA and IIB patients might be found in their different metabolic defects. The fact that fenofibrate's impact on VLDLs is such an important part of its effect on lipoprotein metabolism supports the concept that the effect of circulating fenofibric acid is less pronounced on the LDL receptor in type IIB HLP.

Adult↗

PubMed1996

Increase in magnesium plasma level after orally administered trimagnesium dicitrate.

Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.

Administration, Oral↗

PubMed1996

ISO 14000: Origin, Structure, and Potential Barriers to Implementation.

The ISO 14000 is likely to become the international standard for environmental management. At present, it is an evolving series of individual voluntary standards and guideline reference documents that provide business management with the structure for managing environmental impacts. These encompass environmental management systems, environmental audits, eco-labeling, environmental performance evaluations, life-cycle assessment, and environmental aspects in product standards. The authors present the rationale for the ISO 14000 and the steps in its evolution so far, as well as its present provisions and their implications and its position with regard to regulatory agencies. Particular attention is paid to the consequences of voluntary disclosure and correction of violations. Hanley & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 2 1996 April/June Perspectives on Rural Environmental Health in Central Europe 125 134 EN Tomas Trnovec Burton C. Kross CIREH-Room 352, International Center, University of Iowa, Iowa City, IA 52242, USA. Emil Ginter Life expectancy is about five to seven years less in Central European countries than in comparable countries in Western Europe. Environmental and occupational health risk factors, along with the socioeconomic and political conditions that have prevailed in this region for the past 40 years, are suspected contributing factors to this condition. The initial impression among observers was that environmental pollution by industry was the primary source of contamination leading to human health effects. Current thinking by the authors recognizes that combinations of personal habits, local environmental emissions (home heating), and occupational risk factors are more likely to be influencing the health of this region, particularly in rural areas. A predictive model for standard mortality rates determined that only three potential risk factors were statistically significant: consumption of alcoholic beverages, consumption of citrus fruits, and consumption of cereals. Additional emphasis should be placed on defining risk factors in rural areas of Central Europe, and designing intervention strategies to address these factors.

Journal Article↗

PubMed1996

Selective uptake of the anticancer drug bendamustine by liver and kidney tissues following its intravenous administration to mice.

Distribution of 14C-bendamustine following intravenous (i.v.) administration to mice was examined by whole body autoradiographic (WBAR) and quantitative techniques. The WBAR study showed that 14C-bendamustine-derived radioactivity was distributed extremely unevenly at each time interval investigated. After 5 min of administration the highest density of radioactive material was found in the liver and in the kidney. At all time intervals investigated the brain remained free of the label. In a detailed quantitative distribution study it was found that 14C-bendamustine-derived radioactivity was also unevenly distributed throughout the mouse tissues. At 5 min postdosing the level of 14C was by one order higher in the liver and in the kidney in comparison to the lungs, heart, spleen, and muscle. The results of both WBAR and quantitative tissue distribution studies suggest that bendamustine was selectively taken up from the blood by liver and kidney tissues. Because of this pharmacokinetic property, dose modification should be taken into consideration when administering the drug to patients suffering from hepatobiliary and kidney disorders.

Animals↗

PubMed1996

Role of hepatovasculature in warm ischaemia-reperfusion injury of rat liver.

Liver haemodynamics were studied after warm (37 degrees C) ischaemia of isolated rat livers for periods of 30 s (Group 1), 30 min (Group 2), and 60 min (Group 3) using a constant pressure system with a recirculating blood-free perfusate. Portal flow recovered to basal values within 6 min in livers from Group 1, whereas it was significantly reduced in Group 2 during the initial 15 min and in Group 3 during the first 33 min of reperfusion. Thus, the recovery of liver flow was proportional to the duration of ischaemia. By using the same mode of liver perfusion, the effect of norepinephrine on portal resistance was also studied in normal livers. At the beginning of reperfusion, the values of portal resistance in ischaemic livers were comparable to the values of portal resistance mediated by norepinephrine at concentrations between 10(-7) and 10(-6) mol/l in normal livers. The results suggest that vasoconstriction of the hepatovasculature may be a contributing factor to the reperfusion injury of the liver following warm ischaemia.

Animals↗

PubMed1995

Stereoselective binding of isradipine to human plasma proteins.

Isradipine (PN 200-110) is a highly potent calcium entry blocker with an asymmetrically substituted dihydropyridine ring (methyl- and isopropylester, respectively). The binding of the (+)-(S)-isradipine and (-)-(R)-isradipine to isolated human serum albumin (HSA, 30 mumol/l) and alpha 1-acid glycoprotein (AAG, 10 mumol/l) has been studied in vitro over a wide range of isradipine concentrations (0.06-20 mumol/l) using high-performance liquid chromatography (HPLC). HPLC experiments revealed that both isradipine enantiomers were bound to one class of high-affinity binding sites on the AAG molecule (n(S) = 0.83 +/- 0.05, Ka(S) = (1.33 +/- 0.25) x 10(6) l/mol, n(R) = 0.85 +/- 0.07, Ka(R) = (1.17 +/- 0.44) x 10(7) l/mol). The (R)-enantiomer also exhibited an interaction with the secondary low-affinity binding sites (n'Ka'(R) = (2.66 +/- 0.65) x 10(4) l/mol). In contrast, the pharmacologically more potent (+)-(S)-enantiomer was more strongly bound to HSA than its optical antipode (n(S) = 1.07 +/- 0.07, Ka(S) = (1.76 +/- 0.26) x 10(5) l/mol, nKa(R) = (3.62 +/- 0.06) x 10(4) l/mol). In general, the resulting binding characteristics of individual isradipine enantiomers showed stereoselectivity, but this was opposite for the two most important plasma binding proteins. The process of accumulation of isradipine by human platelets in the therapeutically relevant range (10-80 ng/ml) at 37 degrees C was devoid of stereoselectivity.

Binding Sites↗

PubMed1995

Uptake, reflux, and excretion of bromosulfophthalein in ischaemia-reperfusion injury of rat liver.

The uptake, reflux and excretion of bromosulfophthalein (BSP) were studied on a model of total warm ischaemia for 30 min (group 1) or 60 min (group 2) followed by reperfusion for 45 min in the isolated perfused rat liver of unfasting rats. In group 1, the BSP hepatic uptake was comparable to control livers (30 s ischaemia plus 45 min reperfusion), but was significantly reduced in group 2. The reflux of BSP from liver to perfusate in group 1 and group 2 resulted in the appearance of secondary concentration time peaks of BSP in the reservoir perfusate. This result suggests that ischaemia-reperfusion induced a qualitative change in BSP pharmacokinetics. Excretion of the dye into bile was significantly impaired in group 2 only. The leakage of lactate dehydrogenase into the perfusate was increased moderately in both group 1 and group 2 in comparison to the controls, suggesting a low degree of liver parenchymal injury. In conclusion, the results of this investigation showed that BSP pharmacokinetics were not only undergoing quantitative changes but also a qualitative change in the model of ischaemia-reperfusion injury of the liver obtained from fed rats and may thus serve as a highly sensitive indicator of liver viability.

Animals↗

PubMed1994

Determination of chlorinated phenols and cresols in human urine using solid-phase extraction and gas chromatography.

A method is described for the isolation, derivatization, separation and determination of chlorinated phenols and cresols in urine. After acid hydrolysis, solid-phase extraction on Separcol SI C18 was used. Quantification was based on the internal standard method using 2,6-dibromophenol. Before GC determination the isolated compounds were derivatized with pentafluorobenzyl bromide. The separation of interfering substances followed on a Ekosorb column using elution with dichloromethane-toluene (15:85). The recovery of the method ranged from 72.3 +/- 9.9 to 109.9 +/- 6.3% and the limit of determination varied from 0.0005 to 0.002 micrograms ml-1. Using this method, 52 persons from occupationally and non-occupationally exposed groups were examined for the presence of chlorinated compounds in urine. The levels of chlorinated phenols and cresols were several times higher in the group of occupationally exposed workers, especially for 2,4-dichlorophenol.

Chemical Industry↗

PubMed1994

Modeling of the saturable time-constrained amoxicillin absorption in humans.

Amoxicillin pharmacokinetics was modeled using a two-compartment disposition model and a saturable time-constrained absorption model with a storage compartment. The absorption model parameters estimated by the nonlinear regression are: a rate constant of the systemic input, ksys, (median: 1.31 h-1, range: 0.79-7.01 h-1), a maximal absorption rate, Vmax (median: 1407 mg/h, range: 703-4181 mg/h), an account corresponding to the half maximal rate, Kma, (median: 1077 mg, range: 235-4376 mg), time of the absorption cessation, Tabs, (median: 1.72 h, range: 0.82-4.53 h) and absorption lag time. Tlag, (median: 0.085 h, range: 0-0.123 h). It was shown, that the first-order absorption parallel to the saturable process is negligible in the dose range studied. The model described well the dependence of areas under concentration-time curves on the dose determined in several earlier studies. It was used also to predict the fraction of the amoxicillin dose absorbed for different doses. Simulations performed over a wide dose range (50-10000 mg) demonstrated that the fraction absorbed decreases nonlinearly from 90% at 50 mg to 22% at 10000 mg and strongly depends on the duration of the absorption period.

Absorption↗

PubMed1994

Comparative effects of a Mg-enriched diet and different orally administered magnesium oxide preparations on ionized Mg, Mg metabolism and electrolytes in serum of human volunteers.

OBJECTIVE: To determine whether: 1) short-term dietary elevation in magnesium (Mg) intake could alter serum ionized Mg (IMg2+), total Mg (TMg); % ionized Mg (% IMg2+) and other cations; and 2) different formulated preparations of Mg oxide (MgO) in the presence and absence of phosphate could alter serum IMg2+, TMg, % IMg2+ and other cations in Mg-loaded subjects. METHODS: A randomized, triple cross-over study was performed on a rigorously defined group of normal male volunteers. Eighteen males were administered diets containing four to five times the United States recommended daily allowance (USRDA) of Mg followed by a randomization of three different MgO preparations, in the presence or absence of phosphate, containing equimolar amounts (12.34 mmol) of elemental Mg. Forty age-matched volunteers served as reference range controls. Specific ion selective electrodes were utilized to measure IMg2+, ionized calcium (ICa2+), sodium (Na+) potassium (K+) and hydrogen ion concentration (H+). Measurement of urinary excretion of Mg as well as TMg were determined by atomic absorption spectroscopy. RESULTS: Diets enriched with different oral formulations of Mg given for 6 days result in significant elevations in serum IMg2+ and % IMg2+ but not TMg, ICa2+, K+ or H+ in normal subjects. Although such Mg-loaded subjects demonstrate significant elevation in urinary excretion of Mg, no further changes in IMg2+, TMg or any of the serum cations were produced by ingestion of either of the three MgO preparations. Subjects showing normally low basal levels of serum IMg2+, (< or = 0.54 mM/L), could easily have their serum IMg2+ level manipulated by diets enriched with Mg, whereas subjects having average normal or high normal IMg2+ levels did not have their IMg2+ elevated significantly with either diets enriched with Mg or with exogenous MgO. CONCLUSION: These results indicate that since serum IMg2+ and % IMg2+, but not TMg, can be altered by dietary intake, previous or future findings which may indicate no change in TMg by diet may not reflect changes in biologically-active Mg.

Adolescent↗

PubMed1994

Dose-ranging study of NG-nitro-L-arginine pharmacokinetics in rats after bolus intravenous administration.

1. NG-nitro-L-arginine (10, 30 and 100 mg/kg) was administered intravenously to the male Wistar rat. Plasma was collected over 48, 72 and 120 h and was analysed for the drug by hplc. Pharmacokinetic parameters were calculated using a non-compartmental method. 2. Drug concentration-time profiles of individual rats after all doses studied exhibited secondary peaks, while geometric mean concentration-time curves showed plateaus. 3. NG-nitro-L-arginine plasma concentrations divided by dose almost coincided. Pharmacokinetic parameters were not dose-dependent in the range of 10-30 mg/kg, but changed after 100 mg/kg of NG-nitro-L-arginine indicating some decline from linearity. 4. NG-nitro-L-arginine is a low-extracted drug in rat as the total clearance was low (0.05-0.07 l/h/kg). Half-life and mean residence time were found to be long (17-30 and 23-40 h, respectively). Despite its low lipophilicity, NG-nitro-L-arginine exhibited large steady-state and terminal volumes of distribution (1.4-2.2 l/kg and 1.4-2.4 l/kg, respectively). Together with the double peak phenomenon, these results may be explained by assuming NG-nitro-L-arginine is involved in a recirculation process in the body.

Animals↗