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Pharmacodynamic Interaction (pharmacodynamic + interaction)
Selected AbstractsPharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2002Abhijit Chakraborty Abstract Prednisolone, a commonly used synthetic corticosteroid, and IL-10, a cytokine under investigation for strong antiinflammatory properties, are being contemplated as a potential joint therapeutic regimen in immune disorders. Their pharmacodynamic interactions were examined in blood from healthy adult male and female volunteers using an in vitro phytohemagglutinin (PHA)-stimulated whole,blood lymphocyte proliferation technique. Isobolograms along with parametric competitive and noncompetitive interaction models were used to determine the nature and intensity of interactions. Single drug effects show prednisolone more efficacious in inhibiting lymphocyte proliferation with an IC50 of 3.3 ng/mL and Imax value of 1, signifying complete suppression. Analogous parameters for IL-10 were 16.2 ng/mL for IC50 and 0.89 for Imax. There were no significant differences in the single drug immunosuppressive effects among genders. Their joint effects showed additive interaction based on isobolographic analysis. Parametric analysis using the competitive interaction model described their interaction as slightly synergistic, while the noncompetitive interaction modeling indicate a small degree of antagonism. Also, the joint effects in females tend to be more antagonistic than males. Concomitant use of prednisolone and IL-10 should thus reflect the net additive responses to concentrations of each agent. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1334,1342, 2002 [source] Pharmacodynamic interaction of captopril with garlic in isoproterenol-induced myocardial damage in ratPHYTOTHERAPY RESEARCH, Issue 5 2010Syed Mohammed Basheeruddin Asdaq Abstract It is known that various preparations of garlic and angiotensin-converting enzyme (ACE) inhibitor such as captopril (CAP) have beneficial effects on the left ventricular function and cardiovascular events after myocardial infarction (MI) when used individually. There is no reported interaction between garlic homogenate (GH) and CAP during and after acute MI. Thus the purpose of the current study was to evaluate the possible pharmacodynamic interaction of GH with CAP on isoproterenol (ISO)-induced myocardial damage in rat. Female Wistar albino rats were treated with GH at three different doses of 125; 250 and 500,mg/kg orally for 30 days and CAP (30,mg/kg, p.o.) was incorporated in the interactive groups during the last seven days of GH treatment. Myocardial damage was induced by administration of ISO (150,mg/kg, s.c.) for two consecutive days. Biochemical parameters were studied in serum and heart tissue homogenate of all animals. The GH 250,mg/kg was found to dislodge the effect of ISO on superoxide dismutase and catalase and retained the activities of LDH and CK-MB. Incorporation of CAP during GH treatment provided further protection to myocardium from injury. However, higher dose of GH alone or with CAP failed to prevent damaging effect of ISO. Histopathological determinations confirmed biochemical findings. Thus it is concluded that the combination needs to be used carefully when garlic is consumed at high doses. Copyright © 2009 John Wiley & Sons, Ltd. [source] Pharmacodynamic interactions between recombinant mouse interleukin-10 and prednisolone using a mouse endotoxemia modelJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2005Abhijit Chakraborty Abstract The pharmacodynamic interactions between recombinant mouse interleukin-10 (IL-10) and prednisolone were examined in lipopolysaccharide (LPS)-induced experimental endotoxemia in Balb/c mice. Treatment phases consists of single doses of IL-10 (10 ,g/kg i.p.), prednisolone (25 (mg/kg i.p.), IL-10 (2.5 ,g/kg i.p.) with prednisolone (6.25 mg/kg i.p.), or placebo (saline). Measurements included plasma steroid kinetics and IL-10 concentrations and responses to LPS including proinflammatory cytokines (TNF-,, IFN-,) and circulatory NO measured as plasma nitrate/nitrite concentrations. The intraperitoneal dosing of LPS produced large and transient elevations of plasma TNF-,, IFN-,, and NO concentrations. Noncompartmental and model fitting using extended indirect response models based on drug inhibition of multiphase stimulation of biomarkers by LPS were used to describe the in vivo pharmacodynamics and drug interactions. Dosing with prednisolone, IL-10, or their combinations produced strong inhibition of cytokine and NO production. The IC50 values of prednisolone ranged from 54 to 171 ng/mL, and IC50 values for IL-10 ranged from 0.06 to 0.69 ng/mL. The production of NO was described as a cascading consequence of the TNF-, and IFN-, plasma concentrations. The joint dosing of IL-10 with prednisolone produces moderately synergistic immunosuppressive effects in this system. Both drugs were sufficiently protective in suppressing the inflammatory mediators when administered prior to the LPS trigger, while such effects were modest when administered after the inflammatory stimulus was provoked. The integrated and complex pharmacokinetic/pharmacodynamic models well capture the in vivo processes, drug potencies, and interactions of IL-10 and prednisolone. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:590,603, 2005 [source] Pharmacodynamic Analysis of the Interaction between Tiagabine and Midazolam with an Allosteric Model That Incorporates Signal TransductionEPILEPSIA, Issue 3 2003Daniël M. Jonker Summary: ,Purpose: The objective of this study was to characterize quantitatively the pharmacodynamic interaction between midazolam (MDL), an allosteric modulator of the ,-aminobutyric acid subtype A (GABAA) receptor, and tiagabine (TGB), an inhibitor of synaptic GABA uptake. Methods: The in vivo concentration,response relation of TGB was determined through pharmacokinetic/pharmacodynamic (PK/PD) modeling. Rats received a single intravenous dose of 10 mg/kg TGB in the absence and the presence of a steady-state plasma concentration of MDL. The EEG response in the 11.5- to 30-Hz frequency band was used as the pharmacodynamic end point. Results: Infusion of MDL resulted in a mean steady-state plasma concentration of 66 ± 3 ng/ml. A significant pharmacokinetic interaction with TGB was observed. MDL inhibited TGB clearance by 20 ± 7 ml/min/kg from the original value of 89 ± 6 ml/min/kg. However, no changes in plasma protein binding of both drugs were observed. The concentration,EEG relation of TGB was described by the sigmoid- Emax model. The pharmacodynamic parameter estimates of TGB were: Emax = 327 ± 10 ,V, EC50 = 392 ± 20 ng/ml, and nH = 3.1 ± 0.3. These values were not significantly different in the presence of MDL. Factors that may explain the lack of synergism were identified by a mechanism-based interaction model that separates the receptor activation from the signal-transduction process. High efficiency of signal transduction and the presence of a baseline response were shown to diminish the degree of synergism. Conclusions: We conclude that the in vivo pharmacodynamic interaction between MDL and TGB is additive rather than synergistic. This strongly suggests that allosteric modulation of the antiseizure activity of a GAT-1 inhibitor by a benzodiazepine does not offer a therapeutic advantage. [source] Serotonin syndrome caused by interaction between citalopram and fentanylJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2007S. Ailawadhi MD Summary Objective:, To report a case of serotonin syndrome associated with interaction between fentanyl and citalopram, as evidenced by medication history, clinical features and reversal following discontinuation of fentanyl. Case Summary:, A 65-year-old patient chronically treated with the selective serotonin reuptake inhibitor (SSRI) citalopram developed confusion, agitation, tachycardia, tremors, myoclonic jerks and unsteady gait, consistent with serotonin syndrome, following initiation of fentanyl, and all symptoms and signs resolved following discontinuation of fentanyl. Based on the Naranjo probability scale, serotonin syndrome was a probable adverse reaction associated with co-administration of citalopram and fentanyl. Discussion:, Serotonin syndrome is a potentially lethal pharmacodynamic interaction between medications that increase serotonergic transmission at the synaptic junction. The development of new pharmacological agents with varied properties and actions has increased the risk of serotonin syndrome as a clinical diagnosis. SSRIs and fentanyl are commonly co-administered, especially in the setting of chronic or malignant pain, as underlying depression may contribute to the pathogenesis of pain. Conclusion:, Healthcare professionals should be aware of the possible development of serotonin syndrome as a complication of initiation of fentanyl and other phenylpiperidine opioids in patients treated with SSRIs. [source] The influence of lithium on the antidiuretic effect of desmopressinJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2002Torbjörn Callréus ABSTRACT The objective of this study was to investigate the graded influence from lithium on the antidiuretic effects of desmopressin. Eight healthy male subjects participated in this open, randomised cross-over study with two periods comprising 6 days each. For each subject, one of the study days (6th day) was preceded by a period of lithium treatment. On the study days the subjects were orally water loaded to achieve a state of overhydration with a high urine flow rate. When a steady-state diuresis was achieved after approximately 2 h, 0.396 ,g of desmopressin was administered intravenously as a bolus injection. An indirect-response model, where desmopressin was assumed to inhibit the elimination of response, was fitted to the urine osmolarity data. The effects of the independent variables, Uflow (baseline) (baseline urine flow rate), R0 (baseline osmolarity) and serum lithium concentration, on IC50 (concentration producing 50% of the maximum inhibition) could be expressed by multiple linear regression. In conclusion, we found that an indirect-response model can be a useful tool in investigating and describing the pharmacodynamic interaction between drugs, in this particular case, between lithium and desmopressin. [source] Pharmacodynamic interaction of captopril with garlic in isoproterenol-induced myocardial damage in ratPHYTOTHERAPY RESEARCH, Issue 5 2010Syed Mohammed Basheeruddin Asdaq Abstract It is known that various preparations of garlic and angiotensin-converting enzyme (ACE) inhibitor such as captopril (CAP) have beneficial effects on the left ventricular function and cardiovascular events after myocardial infarction (MI) when used individually. There is no reported interaction between garlic homogenate (GH) and CAP during and after acute MI. Thus the purpose of the current study was to evaluate the possible pharmacodynamic interaction of GH with CAP on isoproterenol (ISO)-induced myocardial damage in rat. Female Wistar albino rats were treated with GH at three different doses of 125; 250 and 500,mg/kg orally for 30 days and CAP (30,mg/kg, p.o.) was incorporated in the interactive groups during the last seven days of GH treatment. Myocardial damage was induced by administration of ISO (150,mg/kg, s.c.) for two consecutive days. Biochemical parameters were studied in serum and heart tissue homogenate of all animals. The GH 250,mg/kg was found to dislodge the effect of ISO on superoxide dismutase and catalase and retained the activities of LDH and CK-MB. Incorporation of CAP during GH treatment provided further protection to myocardium from injury. However, higher dose of GH alone or with CAP failed to prevent damaging effect of ISO. Histopathological determinations confirmed biochemical findings. Thus it is concluded that the combination needs to be used carefully when garlic is consumed at high doses. Copyright © 2009 John Wiley & Sons, Ltd. [source] Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2002Abhijit Chakraborty Abstract Prednisolone, a commonly used synthetic corticosteroid, and IL-10, a cytokine under investigation for strong antiinflammatory properties, are being contemplated as a potential joint therapeutic regimen in immune disorders. Their pharmacodynamic interactions were examined in blood from healthy adult male and female volunteers using an in vitro phytohemagglutinin (PHA)-stimulated whole,blood lymphocyte proliferation technique. Isobolograms along with parametric competitive and noncompetitive interaction models were used to determine the nature and intensity of interactions. Single drug effects show prednisolone more efficacious in inhibiting lymphocyte proliferation with an IC50 of 3.3 ng/mL and Imax value of 1, signifying complete suppression. Analogous parameters for IL-10 were 16.2 ng/mL for IC50 and 0.89 for Imax. There were no significant differences in the single drug immunosuppressive effects among genders. Their joint effects showed additive interaction based on isobolographic analysis. Parametric analysis using the competitive interaction model described their interaction as slightly synergistic, while the noncompetitive interaction modeling indicate a small degree of antagonism. Also, the joint effects in females tend to be more antagonistic than males. Concomitant use of prednisolone and IL-10 should thus reflect the net additive responses to concentrations of each agent. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1334,1342, 2002 [source] Drug Interactions between Antiretroviral Medications and Medications Used in the Treatment of Drug Addiction: Research NeedsTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2010Jag H. Khalsa PhD Today substance dependence is one of the major public health problems in the world with millions of people abusing legal and illegal drugs. In addition, almost one-third of the world's population suffers with one or more infections. Both drugs of abuse and infections are associated with serious medical and health consequences, some of which may be exacerbated by the occurrence of pharmacokinetic and/or pharmacodynamic interactions between medications used in the treatment of these conditions when they co-occur. This review briefly discusses issues surrounding clinical management related to drug interactions experienced by substance abusing patients. The emphasis of this paper is on the research needed to further study the extent, nature, and underlying molecular/genetic mechanism(s) of interactions between drugs of abuse, medications used in the treatment of drug addiction, and co-occurring infections.,(Am J Addict 2009;19:96,100) [source] | ||||||||||