ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01893.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01894.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Transdermal drug delivery system has been in existence for a long time. In the past, the most commonly applied systems were topically applied creams and ointments for dermatological disorders. The occurrence of systemic side‐effects with some of these formulations is indicative of absorption through the skin. A number of drugs have been applied to the skin for systemic treatment. In a broad sense, the term transdermal delivery system includes all topically administered drug formulations intended to deliver the active ingredient into the general circulation. Transdermal therapeutic systems have been designed to provide controlled continuous delivery of drugs via the skin to the systemic circulation. The relative impermeability of skin is well known, and this is associated with its functions as a dual protective barrier against invasion by micro‐organisms and the prevention of the loss of physiologically essential substances such as water. Elucidation of factors that contribute to this impermeability has made the use of skin as a route for controlled systemic drug delivery possible. Basically, four systems are available that allow for effective absorption of drugs across the skin. The microsealed system is a partition‐controlled delivery system that contains a drug reservoir with a saturated suspension of drug in a water‐miscible solvent homogeneously dispersed in a silicone elastomer matrix. A second system is the matrix‐diffusion controlled system. The third and most widely used system for transdermal drug delivery is the membrane‐permeation controlled system. A fourth system, recently made available, is the gradient‐charged system. Additionally, advanced transdermal carriers include systems such as iontophoretic and sonophoretic systems, thermosetting gels, prodrugs, and liposomes. Many drugs have been formulated in transdermal systems, and others are being examined for the feasibility of their delivery in this manner (e.g., nicotine antihistamines, beta‐blockers, calcium channel blockers, non‐steroidal anti‐inflammatory drugs, contraceptives, anti‐arrhythmic drugs, insulin, antivirals, hormones, alpha‐interferon, and cancer chemotherapeutic agents). Research also continues on various chemical penetration enhancers that may allow delivery of therapeutic substances. For example, penetration enhancers such as Azone may allow delivery of larger‐sized molecules such as

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01895.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01896.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The Journal of Clinical Pharmacology is publishing an educational series dealing with Innovative Teaching programs in Clinical Pharmacology. Claire M. Lathers, PhD, FCP, and Alphonse J. Ingenito, PhD, FCP, are coediting this series of articles. Two articles have been published to date. The first is coauthored by AJ Ingenito, CM Lathers, and HJ Burford, and is entitled “Instruction in Clinical Pharmacology: Changes in the Wind” (J Clin Pharmacol1989;29:7–17) and the second was written by CM Lathers and CM Smith and is entitled “Teaching Clinical Pharmacology: Coordination with Medical Pharmacology Courses” (J Clin Pharmacol1989;29:581–597). The third article, “Incorporation of Clinical Pharmacology into the Fourth Year of the Medical Curriculum: Teaching Clinical Pharmacology Without a Clinical Pharmacologist,” (J Clin Pharmacol1990;30:1065–1073) was written by Patricia Williams, PhD at Eastern Virginia Medical School. The fourth article (in press) written by Duncan E. Hutcheon, MD, FCP of UMDNJ in Newark, and Hoda Wadie El‐Gawly, MD, PhD, from the University of Suez, describes a computer‐based problem‐solving system in clinical pharmacology.A system that isn't innovating is a system that is dying. In the long run, the innovators are the ones who rescue all human ventures from death by decay. So value them. You don't have to be one yourself, but you should be a friend of the innovators around you. And if you don't have any around you, you

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01897.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Renal tubular transport of organic anions and cations is assumed to be mutually exclusive. However, results of a number ofin vitroandin vivostudies suggest an interaction between the organic anion, probenecid, and various organic cations in the proximal renal tubule. To evaluate the clinical importance of such an interaction, the authors investigated the pharmacokinetics and pharmacodynamics of procainamide, an organic cation with a low therapeutic index that is excreted in part by active secretion in the proximal tubule, in the presence and absence of probenecid. In a randomized crossover study, six healthy subjects received a single 750‐mg N dose of procainamide, with and without prior probenecid administration (2 g orally). Blood and urine samples were obtained and pharmacokinetic parameters of procainamide were determined in each treatment period. QT intervals were measured from ECG recordings that were obtained at blood collection times for pharmacodynamic evaluation. Coadministration of probenecid did not result in any significant change in the overall disposition of procainamide. In particular, renal clearance was not significantly different (488 ± 95 mL/min without probenecid vs. 478 ± 69 mL/min in the presence of probenecid). Our data suggest an interaction between probenecid and procainamide in the proximal renal tubule does not exit. Reasons for this lack of interaction are discus

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01898.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Recainam is a novel class I antiarrhythmic agent with electrophysiologic characteristics of all three subclasses. The authors evaluated the absolute bioavailability and dose proportionality of three oral doses and two 2‐stage intravenous (IV) infusion doses. Single oral doses of 200, 400, and 800 mg and IV infusions consisting of 0.8 mg/kg/5 min + 1.2 mg/kg/hr (3.75 mg/kg) and 1.6 mg/kg/5 min + 1.2 mg/kg/hr for 4 hours and 55 minutes (7.50 mg/kg) were administered to 15 healthy men. Plasma and urine samples were collected during the 36‐hour period after drug administration and analyzed for recainam concentrations by HPLC. No significant differences were found in any of the pharmacokinetic parameters between the two IV dosage regimens. The absolute bioavailability of orally administered recainam increased from 73% for the 200 mg dose to 81% and 84% for the 400 and 800 mg doses, respectively. Dose proportionality deviated from linearity by 13% for the 200 vs. 400 mg doses, and 10% for the 400 vs. 800 mg doses. The slight deviation from linearity was apparently caused by increased absorption at the higher oral doses. The slight disproportionality in the disposition of recainam is not expected to be clinically signific

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01899.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The present study clarified the effect of disopyramide on left‐ventricular function in patients with hypertrophic cardiomyopathy (5 obstructive type: HOCM, 21 non‐obstructive type: HNCM). The systolic and early diastolic time intervals were assessed 3 hours after a single oral administration of 100‐mg disopyramide. The following parameters were evaluated at rest and after administration of disopyramide: 1) left‐ventricular ejection time index (LVETI), 2) pre‐ejection period index (PEPI), 3) the interval from aortic component of the second heart sound to mitral valve opening (IIA‐MVO), and 4) the interval from MVO to O point of apexcardiogram (MVO‐O). LVETI in HNCM did not change after disopyramide but that in HOCM was significantly shortened (P<.05). PEPI in both HOCM and HNCM was significantly prolonged after administration of disopyramide. IIA‐MVO time in both HOCM and HNCM was not influenced by disopyramide. MVO‐O time in both HOCM and HNCM was significantly shortened after disopyramide. These results suggest that 1) shortening of LVETI in HOCM after disopyramide seemed to be due to the decrease in pressure gradient, 2) PEPI prolongation after disopyramide reflected the decrease in myocardial contractility, and 3) shortening of MVO‐O time after disopyramide indicated the improvement of left‐ventricular filling. The authors conclude that disopyramide may be an important new therapeutic agent in the treatment of patients with hypert

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01900.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01901.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Moduretic has been reported to inhibit the suppression of plasma norepinephrine (NE) levels by the alpha2adrenoceptor agonist, clonidine. To determine whether plasma volume reduction by hydrochlorothiazide (HCTZ) or antagonism of Na+/H+exchange by amiloride (the constituents of Moduretic) is responsible, the authors performed a modified clonidine suppression test (CST) in nine normal volunteers (aged 25 ± 2 years), pretreated for 1 week with HCTZ 50 mg daily, amiloride 10 mg daily, or placebo, in a randomized, double‐blind, crossover study. Baseline characteristics were identical on all study days, except serum [K+] and weight, which were lowest on HCTZ (3.6 ± 0.2 mEq/L and 78.7 ± 2.5 kg), compared with amiloride (4.2 ± 0.1 mEq/L and 79.9 ± 2.4 kg) and placebo (4.0 ± 0.1 mEq/L and 80.2 ± 2.7 kg, P.20), and decreased significantly during CST. The maximal reduction for each subject averaged 72.7 ± 12.4%, 87.9 ± 3.8%, and 82.9 ± 5.7% for placebo, HCTZ, and amiloride. Clonidine also produced a four to seven‐fold increase in plasma growth hormone levels, reduced salivary flow by about 75%, and increased the level of sedation. There were no differences among the three pretreatment regimens in the effects of clonidine, indicating that diuretic therapy does not need to be systematically discontinued in patient

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01902.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY