SEARCH · PubMed Health

Results for “pharmacodynamics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMedDate not supplied

Pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease. The effect of premedication with cystamine on pharmacodynamics and Pharmacokinetics of nitrazepam.

Pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease (I). Effect of premedication with cystamine on pharmacodynamics and pharmacokinetics of nitrazepam. Acta Physiol. Pol. 1977, 28 (2): 161--168. In the experiments carried out on rats the radiation disease was evoked by exposure to 600 R. The strongest radioprotective action of cystamine was found on the 3-rd day of radiation disease. The tendency to normalization of both the pharmacodynamics (exploring mobility and anticonvulsant action) and pharmacokinetics of nitrazepam in the animals premedicated with cystamine was described.

Animals↗

PubMed1977

Comparison of the pharmacodynamic effects of furosemide and BAY g 2821 and correlation of the pharmacodynamics and pharmacokinetics of BAY g 2821 (muzolimine).

In a biometrically planned, double-blind study on 12 Oedema-free male patients the saluretic effect of muzolimine 30 mg was compared with furosemide 40 mg. The plasma level of muzolimine was determined and correlated with its pharmacodynamics. In terms of excretion during the 12-hour observation period muzolimine 30 mg had as great a cumulative effect as furosemide 40 mg. There was a significant difference in the time-response curve. During the first gwo hours furosemide 40 mg had more saluretic effect than muzolimine 30 mg. Between two and four hours there was no significant difference between the two substances. Between four and six hours, however, muzolimine was somewhat more effective than furosemide, although the difference did not reach the level of significance. After 6 h there was no longer any difference between the two compounds. The half-life of the fall in concentration of muzolimine in plasma was 3.7 up to 10 h after its administration. The time-response curve of the increased urine excretion correlated well with the time course of the concentration of muzolimine in plasma.

Adult↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed1979

Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine.

We propose a model of drug pharmacodynamic response that when integrated with a pharmacokinetic model allows characterization of the temporal aspects of pharmacodynamics as well as the time-independent sensitivity component. The total model can accommodate extremes of effect. It allows fitting of simultaneous plasma concentration (Cp) and effect data from the initial distribution phase of drug administration, or from any non-equilibrium phase. The model postulates a hypothetical effect compartment, the dynamics of which are adjusted to reflect the temporal dynamics of drug effect. The effect compartment is modeled as an additional compartment linked to the plasma compartment by a first-order process, but whose exponential does not enter into the pharmacokinetic solution for the mass of drug in the body. The hypothetical amount of drug in the effect compartment is then related to the observed effect by the Hill equation, a nonlinear sigmoid form. Nonlinear least-squares data fitting is used for parameter estimation. The model is demonstrated on two different sets of Cp and effect data for the drug d-tubocurarine (dTC). In 7 normal subjects, the (mean +/- SD) rate constant for equilibration of dTC effect (paralysis) and Cp is 0.13 +/- 0.04 min-1 and the (mean +/- SD) steady-state Cp required to produce 50% paralysis is 0.37 +/- 0.05 microgram/ml.

Adult↗

PubMed1979

Development of pharmacodynamic tolerance to prozosin in congestive heart failure.

In order to determine and compare the pharmacodynamic responses to single and multiple dose prazosin therapy in cardiac failure, 14 patients with severe low-output heart failure underwent central and regional hemodynamic measurements after random placement in one of two prazosin dosing schedules. A single 5 mg oral dose of prazosin (Group A, no. = 7) significantly increased the cardiac index and stroke volume index while significantly decreasing systemic, pulmonary and pulmonary capillary wedge pressures and vascular resistances. Hepatic plasma flow and limb blood flow increased after the single dose. Striking attenuation of these hemodynamic effects occurred when the same dose was administered after 24 hours of pretreatment with oral prazosin, 2 mg every 8 hours (Group B, no. = 7). The plasma prazosin levels of the two groups, drawn 2 hours after administration, were 24.5 and 30.5 ng/ml, respectively. Repeated administration of prazosin in patients with congestive heart failure results in rapid attenuation of its beneficial central and regional hemodynamic effects. The usefulness of this vasodilator as a preload- and afterload-reducing agent in the clinical setting of chronic congestive heart failure may be limited by the development of pharmacodynamic tolerance.

Administration, Oral↗

PubMed1976

Pharmacodynamics of tubocurarine in humans.

The pharmacodynamics of neuromuscular transmission, following blockade by a single i.v. dose of tubocurarine (dtc) in humans, were simulated from experimental serum dtc concentration versus time data and serum dtc concentration versus percentage recovery data. Good agreement was obtained between the simulated and experimental time course of recovery at five different therapeutic doses. The initial apparent volume of distribution (Vapp) of dtc was approximately the same as the serum volume and appeared to increase with the size of the dose. These results were consistent with the suggestion that a greater fraction of the dose of dtc was distributed in non-vascular spaces or bound to tissue at larger doses. A pharmacodynamic working model using an average Vapp of 2848 ml simulated times up to 40% recovery within 15-20% error for doses of dtc of 0.30 mg/kg or less.

Dose-Response Relationship, Drug↗

PubMed1979

Effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium in the cat.

To investigate the effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium, 120 microgram/kg i.v., cats were anesthetized with either pentobarbital (N = 4), ketamine (N = 4), enflurane (N = 5), or halothane (N = 5). A longer onset time and duration of neuromuscular blockade occurred during enflurane and halothane anesthesia. The apparent elimination half-life was longer and the total voluem of distribution at steady state larger during halothane anesthesia. The plasma concentration of pancuronium required for neuromuscular blockades was less during enflurane than during the other three anesthetics. We conclude that inhalation anesthetics may prolong a neuromuscular blockade by altering both the pharmacokinetics and pharmacodynamics of pancuronium.

Adjuvants, Anesthesia↗

PubMed1979

Pharmacodynamics of stannous chelates administered with 99mTc-labeled chelates.

The pharmacodynamics of several tin compounds were studied in healthy rabbits, rabbits with myocardial infarcts, and isolated myocardial tissue. The results showed that tin chelates of pyrophosphate, HEDP, DTPA, and glucoheptonate are very unstable in vivo, giving rise to free stannous ions. These ions localize mainly in bone, with the rest being primarily excreted in the urine. They also concentrate more in infarcted than in normal myocardium; there they enter the mitochondria. The supernatant of homogenates contains bound and free fractions, demonstrating a subcellular distribution pattern similar to that of calcium ions. Tin chelates have different pharmacodynamics from the corresponding 99mTc chelates.

Animals↗

PubMed1976

Pharmacodynamic and pharmacokinetic drug interactions with coumarin anticoagulants.

Many drugs alter the anticoagulant effect of oral coumarins. It is essential that physicians be aware of interactions leading to increased or decreased anticoagulation or to erratic control. Interacting drugs can be classified as influencing the pharmacodynamics (pharmacological actions) or the pharmacokinetics (absorption, biotransformation, binding to plasma proteins, excretion) of oral coumarin anticoagulants. Significant pharmacodynamic interactions include those with vitamin K, salicylates, oestrogens, anabolic steroids, phenylbutazone and other anticoagulants. Significant pharmacokinetic interactions include those with cholestyramine, barbiturates, phenylbutazone, rifampicin and chloramphenicol. When prescribing coumarins, the physician should be fully aware of a patient's other drug therapy and the patient should be cautioned against adding new drugs without consultation. If changes in drug therapy are necessary, close monitoring of prothrombin time after the change is essential.

Anticoagulants↗

PubMed1978

[Studies on the pharmacodynamic activity of several drug solvents. 1st communication: Diethyleneglycol monoethylether, N,N-diethylacetamide, dimethylsufoxide (author's transl)].

The drug solvents diethyleneglycol monoethylether (Transcutol), N,N-diethylacetamide, and dimethylsulfoxide were examined for their pharmacodynamic properties in the following tests: i.p. toxicity, "sign pattern", inclined screen test, balance rod test, and potentiation of hexobarbitone sleeping time in mice, spasmolytic activity in the guinea pig isolated ileum, and cardiovascular studies in anaesthetized rats, cats and dogs including the i.v. toxicity. Except for the cat, N,N-diethylacetamide exhibited the highest toxicity; this solvent, too, was particularly potent in inducing behavioural changes and in potentiating hexobarbitone sleeping time. In the isolated ileum the solvents showed unspecific spasmolytic activities with histamine, carbachol, or BaCl2 as spasmogens. After i.v. administration in rats, cats, and dogs the solvents caused cardiovascular effects even in very low doses. Based on the pharmacodynamic properties doses are recommended for each solvent which should not be exceeded without control experiments in the laboratory routine. These tolerable doses do not only depend on the species but also on the test concerned.

Acetamides↗

PubMed1978

[Studies on the pharmacodynamic activity of several drug solvents. 2. Glycerin, N-(beta-hydroxyethyl)-lactamide, polyethylene glycol 400].

The drug solvents glycerin, N-(beta-hydroxyethyl)-lactamide, and polyethylene glycol 400 (Lutrol 9) were examined for their pharmacodynamic properties in the following tests: i.p. toxicity, "sign pattern", inclined screen test, balance rod test, and potentiation of hexobarbitone sleeping time in mice, spasmolytic activity in the guinea pig isolated ileum, and cardiovascular studies in anaesthetized rats, cats, and dogs including the i.v. toxicity. In mice and rats glycerin exhibited the highest tocicity as well as the greatest activity in potentiating hexobarbitone sleeping time. In the isolated ileum the solvents showed unspecific spasmolytic activities with histamine, carbachol, and BaCl2 as spasmogens. After i.v. administration in rats, cats, and dogs the solvents caused cardiovascular effects even in very low doses. Based on the pharmacodynamic properties, doses are recommended for each solvent which should not be exceeded without control experiments in the laboratory routine. These tolerable doses do not only depend on the species but also on the test concerned.

Animals↗

PubMed2026

Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults.

Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-∞), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n = 102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-∞)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-∞)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-∞)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC ∼30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC ∼29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n = 6; US-OMA, n = 5; EU-OMA, n = 4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.

Humans↗

PubMed2026

Safety, pharmacokinetics and pharmacodynamics of TQC3721, an innovative, dual PDE3 and PDE4 inhibitor, in healthy subjects and patients with chronic obstructive pulmonary disease: Randomised, double-blind, placebo-controlled phase I and IIa clinical trials.

BACKGROUND AND PURPOSE: TQC3721 is a novel inhaled dual phosphodiesterase (PDE3/4) inhibitor designed to provide bronchodilation and anti-inflammatory effects for chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH: First-in-human randomised, double-blind, placebo-controlled phase I (SAD: 0.2 to 24 mg single dose; MAD: 12 mg once daily (QD) for 7 days in healthy subjects) and phase IIa studies (0.75 to 6 mg once or twice daily for 4 weeks in moderate-to-severe patients with COPD) were conducted. Primary outcomes included safety, pharmacokinetics (PKs) and pharmacodynamics (PDs), change from baseline of forced expiratory volume in the first second [FEV1], and FEV1 at 12 and 24 h post-dose on days 1 and 28. KEY RESULTS: TQC3721 was rapidly absorbed (median Tmax of 0.25 to 0.5 h), mainly by pulmonary absorption rather than gastrointestinal absorption, along with low systemic exposure and lack of significant accumulation. TQC3721 demonstrated favourable safety profiles in healthy subjects and patients with COPD. In patients with COPD, TQC3721 produced rapid and outstanding bronchodilation effect sustained over 12 h post-administration, with FEV1 peaking at approximately 2 h post-dose and returning to baseline levels by 12 h, which supports a twice-daily dosing regimen for the future, and peak FEV₁ improvements ranging from 186 to 272 ml across dose groups after 4 weeks of treatment. Moreover, twice-daily 3 and 6 mg regimens were recommended for further clinical study. CONCLUSIONS AND IMPLICATIONS: Pharmacokinetic features, significant bronchodilation effects and overall favourable safety characteristics support further clinical development of TQC3721 as a potential dual-mechanism therapy for COPD.

Adult↗

PubMed2026

A New Highly Concentrated Insulin Aspart AT278 (500 U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

AIMS: To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 [500 U/mL]; AT278-U500) compared with standard concentration insulin aspart (InsAsp [100 U/mL]; InsAsp-U100) and U500 human regular insulin (HumIns [500 IU/mL]; HumIns-U500). MATERIALS AND METHODS: This single-centre, randomised, double-blind crossover 12-h euglycaemic clamp study was conducted in 41 overweight and obese people with type 2 diabetes (BMI 25.0-38.7 kg/m2) receiving a single subcutaneous dose (0.5 U/kg) of AT278-U500 and InsAsp-U100. HumIns-U500 was consecutively studied open label in a 24-h clamp. RESULTS: AT278-U500 exhibited a significantly faster insulin absorption than InsAsp-U100 and HumIns-U500 (t Early50%Cmax: 9 min vs. 35 min vs. 55 min), leading to a significantly higher glucose-lowering effect within the first hour (AUCGIR,0-60min) compared with both InsAsp-U100 (treatment ratio 2.02 [95% CI 1.64; 2.50]) and HumIns-U500 (3.91 [2.89; 5.27]). When divided by median BMI (29.7 kg/m2), AUCGIR,0-60min was significantly higher with AT278-U500 in both the low-BMI and high-BMI subgroup compared to InsAsp-U100. Linear regression showed a significant inverse relationship between BMI and AUCGIR,0-60min for InsAsp-U100 (slope -0.142, p < 0.0001), whereas AT278-U500 showed no such relationship. Overall insulin exposure was similar for AT278-U500 and InsAsp-U100, while overall glucose-lowering effect was comparable across all three treatments. CONCLUSIONS: AT278-U500 maintains its ultra-rapid onset characteristics independent of BMI, representing the first ultra-rapid U500 option for prandial dosing in insulin-resistant people with type 2 diabetes requiring high-dose therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05754424.

Humans↗

PubMedDate not supplied

Studies on the pharmacokinetics and pharmacodynamics of the beta-adrenergic blocking agent sotalol in normal man.

After intravenous injection, sotalol follows a two-compartment distribution pattern. The processes of distribution and elimination are of first order; the intravenous biological half-life is 6 to 8 hours. The drug is mainly excreted by glomerular filtration via the kidney, and metabolites are not found. Of the pharmacodynamic parameters measured, the isoproterenol-induced changes in heart rate, diastolic blood pressure, and free fatty acid return to baseline values immediately during the injection of the beta blocker. Peripheral arterial circulation, lactate, glucose, and pyruvate respond to the beta blocker after a delay. Besides the compartmental distribution of sotalol, other mechanisms of sotalol such as varying responses of the receptors to sotalol or more sluggish intrinsic kinetics of the decrease of parameters measured have to be considered. The effects of various beta blockers may be qualitatively and quantitatively differentiated on the basis of experiments with our test model using steady-state isoproterenol infusion in humans.

Adult↗

PubMed1977

Pharmacokinetics of beta-methyldigoxin in healthy humans III: Pharmacodynamic correlations.

Significant decreases in left ventricular ejection time and heart rate were observed after the oral and intravenous administration of beta-methyldigoxin. The time course of this action correlated with the time course of beta-methyldigoxin and its active metabolite, digoxin, in their deepest pharmacokinetic compartments and not with their plasma levels. This pharmacodynamic activity peaked (decrease of 6.3% at 0.6 mg iv and 3.5% at 0.3 mg iv; decrease of 3.8% at 0.6 mg po and 4.5% at 0.3 mg po) at about 10 hr, concomitantly with the amounts of beta-methyldigoxin in its deepest compartment and showed a terminal half-life equivalent to the 41 hr for beta-methyldigoxin. The relative peak heights and area under the ejection time-time curves indicated a linear dose-response relationship on intravenous administration and an effect greater than that reported for larger amounts of digoxin. The time course of heart rate action correlated (8.3 and 12.5% decreases with 0.3 and 0.6 mg iv, respectively; 6.5 and 9.5% decreases with 0.3 and 0.6 mg po, respectively) with the time course of beta-methyldigoxin and its metabolite digoxin in shallower pharmacokinetic compartments (peaks at approximately 80 min intravenously and 135 min orally), and significant effects had disappeared by 10 hr after drug administration. This finding indicated that the biophases differ for ejection time and heart rate action. Mean arterial blood pressure could not be correlated with the time course of drug, although a small consistent decrease (4-8%) was observed from 22 to 72 hr after drug administration.

Digoxin↗

PubMed1975

Cholinergic and adrenergic neuroreceptors in urinary tract of female dogs. Evaluation of function with pharmacodynamics.

Our preliminary pharmacodynamic studies on the lower urinary tract of adult female dogs indicate that cholinergic and adrenergic (alpha and beta) neuroreceptors in the urethra appear to coordinate the detrusor and urethral function during micturition. Urethral resistance measured as urethral pressure was easily altered with various pharmacologic agents. However, only bethanechol elicited detrusor response measured as intravesical pressure. The possible clinical usefulness of various drugs is outlined. Our results indicate the therapeutic value of ephedrine sulfate and propranolol in stress urinary incontinence; phenoxybenzamine in neurogenic vesical dysfunction and functional outlet obstruction; phenoxybenzamine plus bethanechol in atonic neurogenic bladder; and imipramine in enuresis.

Adrenergic alpha-Antagonists↗

PubMed1975

Imipramine hydrochloride: pharmacodynamic effects on lower urinary tract of female dogs.

Our study of the pharmacodynamics of imipramine hydrochloride of the female canine lower urinary tract indicates the primary mode of action to be the stimulation of alpha adrenergic neuroreceptors in the bladder neck and urethra. This stimulation results in increased resting urethral pressure, adequate sphincter closure, possibly an increase in the bladder capacity and efficient urinary control. Imipramine had no anticholinergic effect on the bladder and the urethra. It also appears unlikely that in enuretic patients imipramine acts by central augmentation of the adrenergic system. No change was noticed in the intravesical or arterial pressures.

Adrenergic alpha-Agonists↗