Studies on the Metabolic Fate of M17055, a Novel Diuretic (5): Pharmacokinetics and Pharmacodynamics of Unchanged Drug in Rat and Dog After Intravenous Administration of M17055

2002 ◽  
Vol 17 (3) ◽  
pp. 214-220 ◽  
Author(s):  
Hiroyuki Nakajima ◽  
Hiroyasu Naba ◽  
Takeshi Nakanishi ◽  
Kiyohiko Nakai ◽  
Takanori Watanabe ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Metabolic Fate ◽  
Unchanged Drug

scholarly journals Studies on the Metabolic Fate of Flecainide Acetate. (1). Blood Levels, Distribution, Metabolism and Excretion in Rats after Repeated Intravenous Administration.

1999 ◽  
Vol 14 (3) ◽  
pp. 201-213
Author(s):  
Mannen MISHIMA ◽  
Masataka UEDA ◽  
Atsushi TAKAO ◽  
Atsuhiro INABA ◽  
Keiko KAMIYA ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Blood Levels ◽  
Metabolic Fate ◽  
Flecainide Acetate

scholarly journals Polymyxins Nebulization over Intravenous Injection: Pharmacokinetics and Pharmacodynamics-Based Therapeutic Evaluation

2019 ◽  
pp. 1-10
Author(s):  
Md. Jahidul Hasan
Keyword(s):  
Respiratory Tract ◽  
Adverse Drug Reactions ◽  
Intravenous Administration ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Drug Reactions ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Gram Negative ◽  
Tract Infections

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrug-resistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions.  

Pharmacokinetics and Pharmacodynamics of Inhaled  versus Intravenous Morphine in Healthy Volunteers 

2000 ◽  
Vol 93 (3) ◽  
pp. 619-628 ◽  
Author(s):  
Mark Dershwitz ◽  
John L. Walsh ◽  
Richard J. Morishige ◽  
Patricia M. Connors ◽  
Reid M. Rubsamen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Healthy Volunteers ◽  
Drug Delivery System ◽  
Delivery System ◽  
Intravenous Administration ◽  
Pharmacokinetic Model ◽  
Pulmonary Drug Delivery ◽  
Pharmacokinetic Data ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Intravenous Morphine

Background A new pulmonary drug delivery system produces aerosols from disposable packets of medication. This study compared the pharmacokinetics and pharmacodynamics of morphine delivered by an AERx prototype with intravenous morphine. Methods Fifteen healthy volunteers were enrolled. Two subjects were administered four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4 mg over 3 min by intravenous infusion. Thirteen subjects were given twice the above doses, i.e., eight inhalations or 8.8 mg intravenously over 7 min. Arterial blood sampling was performed every minute during administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, and 240 min after administration. The effect of morphine was assessed by measuring pupil diameter and ventilatory response to a hypercapnic challenge. Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models. Results The pharmacokinetic data after intravenous administration were described by a three-exponent decay model preceded by a lag time. The pharmacokinetic model for administration by inhalation consisted of the three-exponent intravenous pharmacokinetic model preceded by a two-exponent absorption model. The authors found that, with administration by inhalation, the total bioavailability was 59%, of which 43% was absorbed almost instantaneously and 57% was absorbed with a half-life of 18 min. The median times to the half-maximal miotic effects of morphine were 10 and 5.5 min after inhalation and intravenous administration, respectively (P < 0.01). The pharmacodynamic parameter ke0 was approximately 0.003 min-1. Conclusions The onset and duration of the effects of morphine are similar after intravenous administration or inhalation via this new pulmonary drug delivery system. Morphine bioavailability after such administration is 59% of the dose loaded into the dosage form.

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