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1.
Eur J Drug Metab Pharmacokinet ; 31(4): 291-8, 2006.
Article in English | MEDLINE | ID: mdl-17315541

ABSTRACT

The primary and secondary objectives of this study were to develop and evaluate the predictability of in vitro-in vivo correlation models for theophylline sustained release (SR) granules. Theophylline SR granules meeting the USP Drug Release Test criteria were prepared using ethyl cellulose (EC) and/or stearyl alcohol (SA) and the wet granulation method. In vitro dissolution studies of granule formulation were performed, and a commercial dosage form was prepared using USP XXIII apparatus II at pH 4.5. Differences and similarities between in vitro dissolution curves were compared using both model-dependent (t-test) and -independent (f1, f2 test) statistical techniques, and it was shown that the three dissolution profiles i.e model-dependent, model-independent, and methods based on ANOVA were very similar. The in vivo performance of the commercial dosage form was tested by oral route using male rabbits and in vitro-in vivo correlations were established. This study indicates that the dosage forms with similar in vitro dissolution profiles may have a similar in vivo performance, and that this performance could be estimated using appropriate correlation equations.


Subject(s)
Technology, Pharmaceutical , Theophylline/chemistry , Administration, Oral , Analysis of Variance , Animals , Cellulose/analogs & derivatives , Cellulose/chemistry , Chemistry, Pharmaceutical , Delayed-Action Preparations , Excipients/chemistry , Fatty Alcohols/chemistry , Linear Models , Male , Models, Chemical , Particle Size , Powders , Predictive Value of Tests , Rabbits , Solubility , Tablets , Technology, Pharmaceutical/methods , Theophylline/administration & dosage , Theophylline/blood , Theophylline/pharmacokinetics , Therapeutic Equivalency
2.
Eur J Drug Metab Pharmacokinet ; 28(4): 301-7, 2003.
Article in English | MEDLINE | ID: mdl-14743972

ABSTRACT

The objective of the current study was to establish and evaluate a new technique to increase the accuracy of the in vitro/in vivo linear correlation of single and multiple dose ultra-sustained release theophylline (USRT) preparation (Xantium) in hospitalized patients. In vitro dissolution data for theophylline were collected for 24 h using a USP I (basket) and USP II (paddle) methods. In vivo plasma concentration data were obtained from 8 patients after administration of either single or multiple doses of theophylline. Both in vitro and in vivo results were evaluated by zero-order, first-order, RRSBW, Hixson-Crowell, Higuchi, Hopfenberg, Langenbucher, modified Langenbucher and (Bt)a kinetic models. The individual linear correlations between each in vitro and in vivo percent results and their kinetic distributions were established and regression equations were obtained. The determination coefficient results of the linear kinetic correlations were found to be 0.994 and 0.997 for single and multiple doses by basket method and 0.992 and 0.998 for single and multiple doses by paddle method, respectively. Furthermore, the results of the linear correlations were found as 0.953 and 0.950 for single and multiple doses by basket method and 0.963 and 0.962 for single and multiple doses by paddle method respectively. Therefore, this study suggested that the accuracy of the linear correlation could be improved signilicantly by using linear kinetic correlation.


Subject(s)
Bronchodilator Agents/administration & dosage , Bronchodilator Agents/pharmacokinetics , Theophylline/administration & dosage , Theophylline/pharmacokinetics , Adult , Capsules , Delayed-Action Preparations , Fluorescence Polarization Immunoassay , Humans , Linear Models , Male , Pulmonary Disease, Chronic Obstructive/metabolism , Solubility
3.
Pharmacol Res ; 44(6): 503-7, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11735357

ABSTRACT

The aim of our study was to investigate the antinociceptive activity of moclobemide on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy. The neuropathy was produced by ligation of the sciatic nerve and nociceptive thresholds were determined 15-21 days after surgery by a modification of the Randall-Sellito method. Group 1 (n= 10) received 0.2 ml peroral (p.o.) saline, Group 2 (n= 10) 5 mg x kg(-1), Group 3 (n= 10) 10 mg x kg(-1) and Group 4 (n= 10) 20 mg x kg(-1) p.o. moclobemide. Nociceptive pressure thresholds were then measured every 20 minutes after drug administration. Analysis of variance, Tukey's test and a paired Student's t-test were employed for statistical analysis. The perorally administered moclobemide (5, 10 and 20 mg x kg(-1)) produced an antinociceptive effect on both lesioned and non-lesioned hind paws ( P< 0.05). However, the analgesic effect on the lesioned paw was significantly more potent than the non-lesioned paw. The peak value ( p) remained constant while the maximal increment between the control threshold and the peak value ( I(max)) was significantly more pronounced for the lesioned paw ( P< 0.001). The results of this study may suggest that moclobemide can be a therapeutic alternative to treat some clinical symptoms in peripheral neuropathic conditions.


Subject(s)
Moclobemide/pharmacology , Monoamine Oxidase Inhibitors/pharmacology , Pain Threshold/drug effects , Sciatic Neuropathy/drug therapy , Vocalization, Animal/drug effects , Analgesics/pharmacology , Animals , Hindlimb , Male , Physical Stimulation , Rats , Rats, Wistar , Sciatic Neuropathy/physiopathology
4.
Eur J Pharmacol ; 390(3): 327-34, 2000 Mar 03.
Article in English | MEDLINE | ID: mdl-10708741

ABSTRACT

We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.


Subject(s)
Arginine/pharmacology , Gentamicins/toxicity , Renal Insufficiency/prevention & control , Administration, Oral , Animals , Creatinine/blood , Enzyme Inhibitors/pharmacology , Kidney/drug effects , Kidney/pathology , Lithium/pharmacokinetics , Lithium/urine , Male , NG-Nitroarginine Methyl Ester/pharmacology , Rats , Renal Insufficiency/chemically induced , Sodium/urine , Urination/drug effects , gamma-Glutamyltransferase/drug effects , gamma-Glutamyltransferase/urine
5.
Life Sci ; 66(17): 1627-37, 2000 Mar.
Article in English | MEDLINE | ID: mdl-11261592

ABSTRACT

The antinociceptive activity of tramadol was investigated on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. Despite the analgesic activity of tramadol was clearly established in motor and sensory responses of the nociceptive system in rats, the effect of this atypical opioid on experimental neuropathic pain models is not investigated. The intraperitoneally injected tramadol (2.5, 5 and 10 mg/kg) produced a potent and dose-dependent antinociceptive effect on both lesioned and non-lesioned hind paws. However, the analgesic effect on the lesioned paw was significantly more potent than the non-lesioned paw. This effect was partially antagonized by intraperitoneally administered naloxone (0.1 mg/kg) suggesting an additional non-opioid mechanism. Our results suggest that tramadol may be useful for the alleviation of some symptoms in peripheral neuropathic conditions


Subject(s)
Analgesics, Opioid/therapeutic use , Nervous System Diseases/complications , Pain/drug therapy , Pain/etiology , Tramadol/therapeutic use , Animals , Male , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Pain Measurement/drug effects , Pressure , Rats , Rats, Wistar , Vocalization, Animal/drug effects
6.
Gen Pharmacol ; 33(1): 83-9, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10428020

ABSTRACT

Because the pain sensation is subjective, it is difficult to evaluate the responses to analgesic drugs. Some analgesics that affect the central nervous system are known to change the pupil diameter. The pupil diameter is a more objective criterion that shows the drug effect. We studied the relation between the pupil diameter and analgesia responses to morphine and antidepressants by using the selective micro-receptor agonist morphine (2 and 4 mg/kg), the noradrenaline reuptake inhibitor desipramine (7.5 and 10 mg/kg), the mixed serotonergic and noradrenergic uptake inhibitor and cholinergic receptor antagonist amitriptyline (2.5 and 5 mg/kg), and the selective serotonin reuptake inhibitor sertraline (2.5 and 5 mg/kg) in mice. Both monocular microscopy to assess pupil measurement and the hot-plate test to assess nociceptive thresholds were used in the same animals. We found that morphine played an important role in both mydriasis and analgesia, whereas amitriptyline and desipramine had a greater effect on pupil response than on nociception. Sertraline produced antinociception without causing a change in pupil diameter. As a result, although the pupil response is an important criterion in evaluating the analgesic effect of morphine, it is not possible to put forward the same criterion for the antidepressant drugs. Because different neurotransmitters are involved in pupil and pain mechanisms of antidepressant drugs, it is difficult to evaluate the analgesic response with the pupil diameter.


Subject(s)
Analgesics, Opioid/pharmacology , Antidepressive Agents/pharmacology , Morphine/pharmacology , Pain/prevention & control , Pupil/drug effects , Amitriptyline/pharmacology , Analgesia , Animals , Desipramine/pharmacology , Male , Mice , Mydriasis , Pain/physiopathology , Pain Measurement , Pain Threshold/drug effects , Sertraline/pharmacology , Time Factors
7.
Life Sci ; 64(15): 1313-9, 1999.
Article in English | MEDLINE | ID: mdl-10227587

ABSTRACT

The effects of tianeptine, a novel and unusual tricyclic antidepressant drug, on tail-flick and hot-plate tests, which are two thermal analgesia evaluating methods, have been investigated in mice. Tianeptine (5 and 10 mg/kg), para-chlorophenylalanine (pCPA) (100 mg/kg) and a combination of pCPA and tianeptine (10 mg/kg) or saline were injected to mice intraperitoneally. pCPA (100 mg/kg) was injected 24 h before tianeptine or saline treatment when it was combined with tinaeptine (10 mg/kg) or tested alone. The tail-flick latencies and hot-plate reaction times of the mice were measured between 15th and 180th minutes following injections. Tianeptine (10 mg/kg) exhibited a significant antinociceptive activity that could be measured by both tests as compared to groups which were treated with saline or pCPA alone between 15th and 180th min of the observation period. The lower dose of tianeptine (5 mg/kg) or pCPA (100 mg/kg) did not produce any significant changes on tail-flick latency or hot-plate reaction time of the mice. However, pretreatment with pCPA completely blocked the antinociceptive effect induced by tianeptine (10 mg/kg) in both tests used in the present study. Furthermore, tianeptine (10 mg/kg) did not cause any significant impairment effects on rotarod performance of the mice. Our results suggested that tianeptine has a prominent thermal antinociceptive activity in mice and that increased serotonergic activity may be responsible for the analgesic effect of tianeptine.


Subject(s)
Analgesics/pharmacology , Antidepressive Agents, Tricyclic/pharmacology , Fenclonine/pharmacology , Pain/physiopathology , Thiazepines/pharmacology , Analysis of Variance , Animals , Drug Interactions , Male , Mice , Motor Activity/drug effects , Reaction Time
8.
Nucl Med Biol ; 26(7): 827-31, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10628564

ABSTRACT

Zopiclone (ZPC) was labeled with 131I by using the halogen exchange method. Temperature and reaction time effects to labeling yields were studied. Infrared, nuclear magnetic resonance, and gas chromatography-mass spectroscopy spectra were undertaken to identify chemical structure. High performance liquid chromatography (HPLC) was performed to determine purity of cold zopiclone. Biodistribution studies were performed on rabbits and rats. 131IZPC was administered intravenously to rabbits. Static images were taken by a Sophy DX Gamma Camera. 131IZPC was also administered intraperitoneally to rats. Activities were counted in a NaI(Tl) scintillation detector for several organs (liver, brain, spleen, lung, blood, fat) after rats were decapitated on different times. Biodistribution profiles were obtained depending on the time.


Subject(s)
Hypnotics and Sedatives/chemical synthesis , Piperazines/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Animals , Azabicyclo Compounds , Brain/metabolism , Hypnotics and Sedatives/pharmacokinetics , Iodine Radioisotopes/chemistry , Isotope Labeling/methods , Male , Piperazines/pharmacokinetics , Rabbits , Radiopharmaceuticals/pharmacokinetics , Rats , Receptors, GABA-A/metabolism , Tissue Distribution
9.
J Ethnopharmacol ; 67(3): 307-12, 1999 Nov 30.
Article in English | MEDLINE | ID: mdl-10617065

ABSTRACT

The aim of the present study was to investigate the antinociceptive activity of Hypericum triquetrifolium Turra. extract. The lyophilized extract was administered to male Swiss mice. Formalin paw test and tail flick tests were used for the evaluation of the antinociceptive activity. Plant extract (10, 25, 50 and 60 mg kg(-1), i.p.) (n = 16-24 for each group) or vehicle (n = 27) was administered 30 min before the subplantar formalin injection. In the tail flick test, mice were examined for latency to withdraw their tails from a noxious thermal stimulus using a tail flick meter (n = 8 for each group). The effects of the extract on sensorimotor performance was also assessed (n = 16-24 for each group). The extract caused a significant dose-related inhibition of the first phase (50, 60 mg kg(-1), i.p.) and second phase (10, 25, 50 and 60 mg kg(-1), i.p.) of formalin induced hindpaw licking. Additionally, the extract administration (50, 60 mg kg(-1), i.p.) increased the tail flick latencies. No significant change was observed in any of the treatment groups in the sensorimotor performance test. The observed antinociceptive activity of the extract may be due to its noradrenaline and serotonin reuptake blocking activity. Moreover, the probable antiinflammatory activity of the extract may play a role in the dose-related inhibition of the second phase of formalin paw test.


Subject(s)
Analgesics/pharmacology , Hypericum/chemistry , Plant Extracts/pharmacology , Plants, Medicinal , Animals , Male , Mice
10.
Int J Clin Pharmacol Res ; 18(1): 21-9, 1998.
Article in English | MEDLINE | ID: mdl-9604731

ABSTRACT

The aim of the present study was to compare the analgesic efficacy of piroxicam-FDDF (fast dissolving dosage form) with naproxen sodium, following bilateral removal of impacted third molars. A double-blind, randomized, crossover, analgesic trial was carried out on 40 patients undergoing surgical removal of one lower third molar at each visit. The analgesic efficacy of a single dose regimen of piroxicam-FDDF (40 mg, Feldene Flash, Pfizer, Turkey) was compared with naproxen sodium (550 mg, Anaprotab, Sanli, Turkey). Pain intensity was measured on a category-rating scale during the 8-h period after drug administration. Each patient evaluated the efficacy of the study medication at 15, 30, 45, 60, 90 and 120 min, and then hourly for up to 8 h of drug ingestion. Additional key efficacy measures were also determined (pain intensity difference [PID], sums of pain intensity difference [SPID], total pain relief [TOTPAR], peak pain relief, number of observations at which pain was half-relieved, overall evaluation of study medication effectiveness, and time to medication with a back-up analgesic). The data were analyzed by paired Student's t-test and one-way analysis of variance (ANOVA). Results are expressed as means +/- SEM, and p < 0.05 was taken as statistically significant. The PID and pain relief scores of the piroxicam-FDDF group were significantly greater than those for the naproxen sodium group at 15, 30, 45 and 60 min (p < 0.01). After 90 min to 8 h, no statistical significance was revealed among the two test groups (p > 0.05). The peak pain relief, maximal analgesic effect, SPID, TOTPAR values, adjusted mean number of observations with pain at least half-relieved, and the final overall evaluation records were all superior for piroxicam-FDDF (p < 0.05). The results of this study clearly show that the analgesic efficacy of piroxicam-FDDF is superior to naproxen sodium in the treatment of pain following oral surgery for the removal of impacted third molars.


Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Naproxen/therapeutic use , Pain, Postoperative/drug therapy , Piroxicam/therapeutic use , Adolescent , Adult , Analgesics/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Double-Blind Method , Female , Humans , Male , Naproxen/adverse effects , Pain Measurement , Piroxicam/adverse effects , Tooth Extraction/adverse effects
11.
J Affect Disord ; 43(1): 5-10, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9127825

ABSTRACT

The beta 2-Mg (beta 2-microglobulin) and GAG (glycosaminogyclan) excretions in 107 patients with bipolar disorder who had been on lithium treatment for 1-15 years were compared with 29 matched psychiatric control patients. 24-h urine volume, urine beta 2-Mg, GAG values were significantly higher, and maximal urinary osmolality was significantly lower in patients on lithium than in controls. No relationship was found between creatinine clearances and duration of illness, duration of lithium treatment and daily lithium dosages. Duration of lithium treatment was not related to the concentrating capacity. The beta 2-Mg excretion rates were significantly higher in patients with manifest polyuria and with severe concentration defect.


Subject(s)
Bipolar Disorder/drug therapy , Kidney Function Tests , Lithium Chloride/adverse effects , Polyuria/chemically induced , Adult , Basement Membrane/drug effects , Bipolar Disorder/urine , Creatinine/urine , Female , Glomerular Filtration Rate/drug effects , Glycosaminoglycans/urine , Humans , Kidney Concentrating Ability/drug effects , Kidney Glomerulus/drug effects , Kidney Tubules, Proximal/drug effects , Lithium Chloride/administration & dosage , Long-Term Care , Male , Middle Aged , Polyuria/urine , beta 2-Microglobulin/urine
12.
Acta Paediatr ; 85(6): 753-4, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8816218

ABSTRACT

The aim of this study was to investigate serum digoxin-like immunoreactive substance (DLIS) levels in 60 healthy term infants when they reached 1-6 months of age with regard to feeding regimen. Group I consisted of 30 infants fed exclusively on breast milk. Groups II and III each consisted of 15 infants fed on formula and cow's milk, and on formula and cow's milk supplemented by breast milk, respectively. Mean serum DLIS concentrations were 0.03 +/- 0.05, 0.18 +/- 0.09 and 0.15 +/- 0.09 ng/ml in groups I-III, respectively. The difference between the DLIS levels in groups II and III was not significant. Serum DLIS levels of infants in groups II and III, on the other hand, were significantly higher than in group I (p < 0.05). These findings were interpreted to suggest that artificial nutrients may cause volume expansion and an increase in endogenous DLIS levels. The latter response is possibly a protective mechanism to decrease volume expansion in groups II and III.


Subject(s)
Bottle Feeding , Breast Feeding , Digoxin , Enzyme Inhibitors/blood , Food, Formulated , Infant Food , Infant, Newborn/blood , Saponins/blood , Blood Volume , Cardenolides , Humans , Infant , Serum Albumin/metabolism , Sodium/blood , Water-Electrolyte Balance
13.
Int J Clin Pharmacol Res ; 16(2-3): 57-65, 1996.
Article in English | MEDLINE | ID: mdl-9063757

ABSTRACT

The search for new effective analgesics without unwanted effects on the coagulation mechanism and a longer duration of activity has been intensified. One such development is diflunisal and the aim of this study was to compare the analgesic effect of diflunisal with that of paracetamol. A combined single dose (500-mg tablets), double-blind, randomized, controlled design in out-patients (n = 104) with moderate or severe pain caused by the surgical removal of impacted mandibular third molars was used in this study. Pain intensity and relief were assessed postoperatively for 8h using category-rating scales. The results showed a statistically significant difference in favour of diflunisal in each and every parameter used in determining the efficacy of the treatment.


Subject(s)
Acetaminophen/therapeutic use , Analgesics, Non-Narcotic/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diflunisal/therapeutic use , Pain, Postoperative/drug therapy , Tooth Extraction , Adolescent , Adult , Double-Blind Method , Female , Humans , Male
14.
Eur J Drug Metab Pharmacokinet ; 20(4): 271-4, 1995.
Article in English | MEDLINE | ID: mdl-8983931

ABSTRACT

Erythrocyte lithium concentration, which is a better predictor of brain lithium levels than plasma lithium concentrations, possesses the disadvantage of precise hourly determination following the last intake. The variability in RBC lithium accumulation increases as the extracellular lithium concentration increases. This increase is also time dependent and it would be very useful if the pharmacokinetic rate constant were known. Unfortunately, low lithium levels do not allow measurements within confidence intervals. In this work, we tried to determine, in vitro, the kinetic rate constants in erythrocytes of healthy volunteers. Different high lithium loaded plasma-like media were used for an extrapolation procedure of constants allowing the determination of an erythrocyte load constant namely K0 = 0.0161 +/- 0.0005 h-1 at corresponding plasma lithium concentrations. The abnormalities of lithium transport determined by in vitro procedures would be very useful in understanding the etiology of affective illness. Lithium flux pre-controls corrected with this rate constant would be very helpful in enlarging laboratory time management.


Subject(s)
Antimanic Agents/blood , Erythrocytes/metabolism , Lithium/blood , Antimanic Agents/pharmacokinetics , Humans , In Vitro Techniques , Lithium/pharmacokinetics
16.
Eur J Drug Metab Pharmacokinet ; 20(2): 129-33, 1995.
Article in English | MEDLINE | ID: mdl-8582438

ABSTRACT

Gastrointestinal motility is one of the most important factors than can influence drug absorption from gastrointestinal tract. The aim of the present study was to investigate the effect of delayed gastric emptying and intestinal transit on pharmacokinetic parameters of lithium. Treatment animals were administered an anticholinergic agent (propantheline bromide, 4 mg/kg, p.o.) 10 min before lithium chloride (1.5 mM/kg, p.o.) administration, whereas the control group was administered the same dose of lithium p.o., alone. Plasma lithium levels were measured by flame spectrophotometry and calculated with a computer programme (SIPHAR). Differences detected in AUC, fractionated AUC values, Cmax and tmax suggest that using delayed absorption process, it is possible to prolong by 272% the plateau time of the drug in the therapeutic range and this approach might be an alternative way to prevent some undesirable effects due to peak plasma levels above the maximal therapeutic level. This approach might be more important as an alternative for suitable slow release formulations.


Subject(s)
Gastric Emptying/physiology , Lithium/pharmacokinetics , Animals , Gastrointestinal Transit/physiology , Intestinal Absorption , Male , Parasympatholytics/pharmacology , Propantheline/pharmacology , Protein Binding , Rabbits
17.
Eur J Drug Metab Pharmacokinet ; 19(4): 319-25, 1994.
Article in English | MEDLINE | ID: mdl-7737233

ABSTRACT

The relative bioavailability of three carbamazepine generics available in Turkey, were investigated in 5 healthy male volunteers. When issuing a license to any drug, FDA stipulates at most a difference of 20% from the reference drug only in peak concentration and AUC (area under the curve). This condition may cause some problems, as two generics of the same drug can yield the same total amount (AUC) and can be accepted as bioequivalent despite different curves of the two drugs. In this study, to compare drugs from the point of view of bioequivalency, we suggest a new calculation method that takes into account ka (absorption rate constant), ke (elimination rate constant), tmax (time to peak), MRT (mean residence time) and AUC. Should this formula be used in comparison of bioequivalency, all the parameters related to the kinetics of drugs will have been taken into account. The suggested parameter is: [formula: see text] However, amongst three carbamazepine generics-Tegretol, Temporol and Karazepin-the most desirable curve is that of Tegretol, while bioavailability values are respectively F = 0.86, 0.93, 0.85 and AUC = 145, 161, 127. The A parameter values are respectively 49.3, 47.2, 42.9.


Subject(s)
Carbamazepine/pharmacokinetics , Adult , Biological Availability , Body Fluid Compartments , Body Weight/physiology , Chemistry, Pharmaceutical , Cross-Over Studies , Humans , Male , Mathematical Computing , Therapeutic Equivalency
18.
Encephale ; 16(3): 203-4, 1990.
Article in English | MEDLINE | ID: mdl-2117522

ABSTRACT

In this study Lewis and ABO-Rh blood group systems were investigated in forty patients with bipolar affective disorder and forty healthy control subjects. The results were discussed in view of the literature.


Subject(s)
ABO Blood-Group System , Bipolar Disorder/blood , Lewis Blood Group Antigens , Rh-Hr Blood-Group System , Adult , Humans , Middle Aged
19.
Experientia ; 32(6): 718-9, 1976 Jun 15.
Article in English | MEDLINE | ID: mdl-181267

ABSTRACT

Under the postulated existence of a mechanism regulating the NREM sleep- REM sleep sequence and a reset of this mechanism by long awakenings, the variability of sleep cycle in the rat was studied. Awakenings of various durations were included in the definition of sleep cycle boundaries. Results show that an intervening awakening of 1 min is close to the limit under which the same cycle seems to be resumed after the awakening and above which the previous cycle is abortive and a new cycle will start after the next sleep onset.


Subject(s)
Sleep Stages , Animals , Circadian Rhythm , Electroencephalography , Male , Rats , Sleep, REM , Wakefulness
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