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G W Amsden

Publications and source records attributed to G W Amsden.

35 records · Page 2Linked to original sources
PubMed1998

Absence of effect of terbinafine on the activity of CYP1A2, NAT-2, and xanthine oxidase.

Terbinafine is an allylamine antifungal agent used for the treatment of onychomycosis. It has previously been reported to interact with caffeine and is metabolized in part by the cytochrome P450 systems. This open-label, randomized, crossover study was conducted to examine the effect of terbinafine on the activity of cytochrome P450 1A2 (CYP1A2), N-acetyltransferase (NAT-2), and xanthine oxidase (XO). Twelve healthy nonsmoking adult volunteers were enrolled. Each received single doses of caffeine (100 mg), and urine was collected for a 16-hour period with and without multiple-dose oral administration of terbinafine (250 mg daily for 3 days). Study periods were separated by a 4-week washout period. Urinary caffeine metabolite ratios were used to assess CYP1A2, NAT-2 and XO activity. Comparison of mean metabolic ratios for treatment with and without terbinafine indicated that terbinafine did not appear to alter the activity of CYP1A2, NAT-2, or XO, all of which regulate the biotransformation of caffeine.

Adult↗
PubMed1998

Effect of terbinafine on theophylline pharmacokinetics in healthy volunteers.

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident.

Adult↗
PubMed1998

Effect of grapefruit juice on clarithromycin pharmacokinetics.

To investigate whether grapefruit juice inhibits the metabolism of clarithromycin, 12 healthy subjects were given water or grapefruit juice before and after a clarithromycin dose of 500 mg in a randomized crossover study. Administration of grapefruit juice increased the time to peak concentration of both clarithromycin (82 +/- 35 versus 148 +/- 83 min; P = 0.02) and 14-hydroxyclarithromycin (84 +/- 38 min versus 173 +/- 85; P = 0.01) but did not affect other pharmacokinetic parameters.

Adult↗
PubMed1998

Oral cimetidine prolongs clarithromycin absorption.

The present study was conducted to identify any potential interaction between oral cimetidine and clarithromycin. Twelve healthy subjects were administered single doses of clarithromycin alone and with oral cimetidine dosed to steady state. Cimetidine prolonged the absorption of clarithromycin, as evidenced by decreased peak concentrations of both clarithromycin and 14-OH-clarithromycin (14OHC) in serum (46 and 43%, respectively), a delay in the formation of 14OHC (increase of 68%), and increases in both of their half-lives (75 and 82%, respectively), despite no changes in total oral clearance or area under the concentration-time curve for either compound. No mechanism for this interaction has been identified.

Absorption↗
PubMed1998

Current issues in onychomycosis.

OBJECTIVE: To review the epidemiology, mycology, clinical features and diagnosis, current pharmacotherapy, and pharmacoeconomics of onychomycosis. DATA SOURCES: We conducted a MEDLINE search from 1966 to May 1997. References from these articles, manufacturers of the discussed antimycotics, and relevant abstracts from recent dermatology conferences were used to collect pertinent data. DATA EXTRACTION: Data were obtained from published controlled studies and case reports. In the pharmacotherapy section, the most weight was placed on fully reported, randomized, controlled comparative trials, but abstracts and case series were included when well-controlled studies were unavailable. DATA SYNTHESIS: Onychomycosis is a common nail disorder that has a substantial impact on patients' quality of life. It is most commonly caused by dermatophytes, but yeasts and molds can also be involved. Diagnosis is made through clinical presentation, potassium hydroxide preparations, and culture of tissue/nail samples. Griseofulvin was the drug of choice for many years, but its low cure rates and the development of newer, more effective drugs made it fall out of favor. Current therapeutic alternatives include fluconazole, itraconazole, and terbinafine. Data on the use of fluconazole are limited to case series and reports. Continuous dosing of itraconazole and terbinafine are well-proven therapies. New data are becoming available on the use of pulse itraconazole dosing, which has recently been approved by the Food and Drug Administration for fingernail infections. These drugs are well tolerated, but attention to drug interactions is necessary with the azoles. CONCLUSIONS: Currently, continuous terbinafine appears to be the most cost-effective drug for dermatophyte onychomycosis.

Antifungal Agents↗
PubMed1997

The role of advanced generation macrolides in the prophylaxis and treatment of Mycobacterium avium complex (MAC) infections.

Since the start of the acquired immunodeficiency syndrome (AIDS) epidemic, the role of Mycobacterium avium complex (MAC) as an opportunistic pathogen in advanced AIDS patients has become more and more clear. Once identified in an advanced AIDS patient it is possible to find evidence that the MAC organism and infection is not only present in the pulmonary tree, but has also disseminated to a wide variety of body organs. Treatment of MAC or disseminated MAC (DMAC) infections has historically been very difficult due to the inherent resistance of the MAC pathogen to most standard antimycobacterial agents. This has resulted in the development of new agents for the prevention of DMAC infection as well as combinations of both new and standard agents for its treatment. Three drugs are currently approved for single-agent DMAC prophylaxis, including rifabutin, azithromycin and clarithromycin. Combinations of agents for DMAC treatment are highly variable in content but most experts agree that all combinations should contain one of the advanced generation macrolides (azithromycin or clarithromycin). Both of these agents have favourable intracellular pharmacokinetics and pharmacodynamics which maximise their effects against this mostly intracellular pathogen. Due to the paucity of comparative data, no one macrolide can be recommended over the other. However, the expected increase in compliance, lower weekly and annual costs, and lack of any drug interactions may make azithromycin a preferable choice, but this should be decided on a case-by-case basis.

Anti-Bacterial Agents↗
PubMed1995

Macrolides versus azalides: a drug interaction update.

OBJECTIVE: To describe the current drug interaction profiles for all approved and investigational macrolide and azalide antimicrobials, and to comment on the clinical impact of these interactions when appropriate. DATA SOURCES: MEDLINE was searched to identify all pertinent studies, review articles, and case reports from 1975 to 1995. When appropriate information was not available in the literature, data were obtained from the product manufacturers. STUDY SELECTION: All available data were reviewed to give an unbiased account of possible drug interactions. DATA EXTRACTION: Data for some of the interactions were not available from the literature, but were available from abstracts or from company-supplied materials. Although the data were not always entirely explicative, the best attempt was made to deliver the pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. DATA SYNTHESIS: Since the introduction of erythromycin into clinical practice, there have been several clinically significant drug interactions identified throughout the literature associated with this drug. These interactions have been caused mostly by inhibition of the CYP3A subclass of hepatic enzymes, thereby decreasing the metabolism of any other agent given concurrently that is also cleared through this mechanism. With the development and marketing of several new macrolides, it was hoped that the drug interaction profile associated with this class would improve. This has been met with variable success. Although some of the extensions of the 14-membered ring macrolides have shown an incidence of interactions equal to that of erythromycin, others have shown improved profiles. In contrast, the 16-membered ring macrolides have demonstrated a much improved, though not absent, interaction profile. The most success in avoiding drug interactions through structure modification has been accomplished with the development of the azalide class, of which azithromycin is the first to be approved for marketing. This agent has to date produced none of the classic drug interactions that most macrolides have demonstrated in patient care. CONCLUSIONS: The introduction of new 14- and 16-membered ring macrolides appears to have had a variable effect in modifying the incidence of drug interactions associated with this class. Azithromycin, a member of the new azalide class, has to date produced fewer clinically significant interactions than other azalides with any agent that is cleared through the CYP3A system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Treatment of non-HIV cryptosporidial diarrhea with azithromycin.

OBJECTIVE: To report a patient with non-HIV-related cryptosporidial diarrhea who was treated effectively with a regimen of high-dose azithromycin therapy. CASE SUMMARY: A 42-year-old immunocompetent man contracted cryptosporidiosis from an ailing calf that he had purchased. He finally was admitted to the hospital because of excessive weight loss and profuse diarrhea. The patient was started on a course of high-dose azithromycin therapy and symptoms resolved within 48 hours. Follow-up stool cultures were negative for the parasite. DISCUSSION: Although usually associated with immunocompromised patients, cryptosporidiosis occurs in immunocompetent hosts in a significant portion of the reported cases each year. Although self-limiting in most cases in this population, the disease can be severe at times and require treatment. Paromomycin therapy has been used in the past with good results. Although macrolides have had erratic effects against this parasite in the past, azithromycin (an azalide) demonstrated good efficacy in this patient. CONCLUSIONS: Azithromycin has demonstrated that it may be an effective option for the treatment of cryptosporidiosis in immunocompromised patients. Studies involving its use in immunocompromised patients are currently underway.

Adult↗
PubMed1994

Pharmacodynamics of bolus famotidine versus infused cimetidine, ranitidine, and famotidine.

A four-way crossover pilot study was conducted to compare the pharmacodynamic response of intermittent famotidine (20 mg every 12 hr) to continuous infusions of cimetidine (1200 mg/24 hr), ranitidine (150 mg/24 hr), and famotidine (40 mg/24 hr) in six normal male volunteers. Intragastric pH was monitored continuously for 24 hours. Comparisons included percent time during the 24-hour period that gastric pH was greater than pH 4.0, and pH 5.0, and also for the steady-state period of each regimen (12-24 hr). Although no statistically significant difference was observed for any of these comparisons, a clinically relevant trend was observed. In crossover experiments, famotidine intermittent infusions provided gastric pH readings above 4.0 and 5.0 for a longer duration than any of the continuous infusion regimens. Famotidine intermittent infusion regimens (20 mg every 12 hr) are at least equivalent to continuous infusions of cimetidine, ranitidine, and famotidine. Based on these findings, comparative studies in an appropriate critical care population would be beneficial, but any such studies must use a crossover design because of the even higher degree of intersubject variance in pH control. For this reason, the normal volunteer crossover model used here may provide important comparative information for the various regimens used in suppression of gastric acidity.

Adult↗
PubMed1992

Trimetrexate for Pneumocystis carinii pneumonia in patients with AIDS.

OBJECTIVE: The primary objective of this article is to introduce readers to the use of a new agent, trimetrexate (TMTX), in the treatment of Pneumocystis carinii pneumonia (PCP). The article also gives the readers an overview of PCP and discusses some of the controversies surrounding it. Pharmacokinetic data and clinical trials are reviewed, as well as adverse effects, drug interactions, and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: As both pharmacokinetic and clinical trials were few in number, all available trials were reviewed. DATA EXTRACTION: Pharmacokinetic data from trials involving patients with AIDS was sparse; therefore, those involving oncology patients, including a pediatric population, were included. Although more trials need to be done in AIDS patients, the results from the oncologic trials give us a baseline from which to extrapolate. All clinical trials available at the time of publication were reviewed as were all of the preliminary results from three ongoing trials, which were made available through a personal communication. DATA SYNTHESIS: TMTX has been found to be 1500 times more potent than trimethoprim as a dihydrofolate reductase inhibitor, and has the potential to provide an effective therapeutic option for PCP. TMTX is a lipid-soluble analog of methotrexate and is thus capable of greater penetration into Pneumocystis cells, which lack the folate membrane transport system necessary to take up classic folate structures like leucovorin and methotrexate, thereby negating any clinical effectiveness of methotrexate and allowing leucovorin to be used for host cell rescue. TMTX's pharmacokinetic parameters best fit a multicompartmental model with a terminal half-life of up to 12 hours. It is cleared both hepatically and renally with up to 41 percent excreted unchanged in the urine. Although TMTX's pharmacokinetic parameters are variable, the need for plasma concentration monitoring at present is unclear, as no dose-response relationship has been established.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Azithromycin: the first azalide antibiotic.

OBJECTIVE: To discuss the chemistry, mechanism of action, spectrum of activity, pharmacokinetics, clinical trials, adverse-effect profile, drug interactions, and dosage guidelines of azithromycin, the first azalide antibiotic. DATA SOURCES: Pertinent literature published between 1988 and the present was identified via a MEDLINE search. Of 77 articles retrieved, 37 have been referenced. STUDY SELECTION: Azithromycin is a new agent, and as such, limited data regarding this drug are available in the literature. We evaluated all pharmacokinetic, microbiologic, and basic science articles pertaining to azithromycin, and reviewed the clinical efficacy trials that we believed were of good quality for each indication for which azithromycin has received approval to date. Comparative clinical trials involving large numbers of patients, clinical outcome assessments, and recommendations for azithromycin use are included. DATA SYNTHESIS: Azithromycin is a macrolide derivative and the first of the 15-membered ring azalide class of antimicrobials. Although its mechanism of action and susceptibility to resistance are similar to those of the macrolide antibiotics, azithromycin's extended spectrum of activity includes gram-positive and gram-negative organisms, as well as atypical pathogens. Azithromycin is stable at gastric pH and has an absolute bioavailability of approximately 37 percent following oral administration. Although its serum concentrations are typically low, the drug concentrates to a high degree in tissue. Azithromycin is cleared primarily by the biliary and fecal routes; its serum half-life is in excess of 60 hours. Several clinical trials have proven that a 5-day course of azithromycin administered once a day is equally efficacious to a 7- to 14-day course of other commonly used oral antimicrobials, administered two to four times a day, for the treatment of upper and lower respiratory tract and skin and skin-structure infections. Urethritis and cervicitis caused by chlamydia are treated with a single 1-g dose. Trials have shown azithromycin's adverse-effect profile to be equal or even superior to that of other agents, with only 0.7 percent of patients discontinuing therapy versus 2.6 percent for comparable drugs. CONCLUSIONS: Azithromycin represents a significant improvement in the treatment of selected community-acquired infections. Although this agent may revolutionize the treatment of sexually transmitted diseases caused by chlamydia, it also should impact the management of respiratory tract and skin and skin-structure infections. Because of its unique pharmacokinetics and excellent adverse-effect profile, patient compliance should be greatly enhanced compared with other commonly used oral antimicrobials. Azithromycin's primary role in the near future will be in the community setting. Although its use in the hospital may be limited, this drug will be a convenient therapeutic option to have on hand in the emergency room and outpatient clinic. Azithromycin may also be used in the future to treat opportunistic infections in immunocompromised patients.

Azithromycin↗
PubMedDate not supplied

Erythromycin, clarithromycin, and azithromycin: are the differences real?

Erythromycin, clarithromycin, and azithromycin are clinically effective for the treatment of common respiratory and skin/skin-structure infections. Erythromycin and azithromycin are also effective for treatment of nongonococcal urethritis and cervicitis due to Chlamydia trachomatis. Compared with erythromycin, clarithromycin and azithromycin offer improved tolerability. Clarithromycin, however, is more similar to erythromycin in pharmacokinetic measures such as half-life, tissue distribution, and drug interactions. Misunderstandings about differences among the macrolides (erythromycin and clarithromycin) and the azalide (azithromycin) in terms of pharmacokinetics and pharmacodynamics, spectrum of activity, safety, and cost are common. The uptake and release of these compounds by white blood cells and fibroblasts account for differences in tissue half-life, volume of distribution, intracellular:extracellular ratio, and in vivo potency. Although microbiologic studies reveal that gram-positive pathogens are equally susceptible to these agents, significantly more isolates of Haemophilus influenzae are susceptible to azithromycin than to erythromycin or clarithromycin. Concentrations achieved at the infection site and duration above the minimum inhibitory concentration are as important as in vitro activity in determining in vivo activity against bacterial pathogens. Analysis of safety data indicates differences among these agents in drug interactions and use in pregnancy. Analysis of safety data reveals pharmacokinetic drug interactions for erythromycin and clarithromycin with theophylline, terfenadine, and carbamazepine that are not found with azithromycin. Both erythromycin and azithromycin are pregnancy category B drugs; clarithromycin is a category C drug. The numerous differences in pharmacokinetics, microbiology, safety, and costs among erythromycin, clarithromycin, and azithromycin can be used in the judicious selection of treatment for indicated infections.

Anti-Bacterial Agents↗
PubMedDate not supplied

Orthostatic hypotension induced by sertraline withdrawal.

Sertraline is a member of the newest class of antidepressants, the selective serotonin reuptake inhibitors. Due to its inherent selectivity and its lack of action with norepinephrine, dopamine, monoamine oxidase, and cholinergic receptors, this drug is unlikely to have any cardiovascular activity. A patient receiving sertraline for depression developed dizziness and orthostatic hypotension on repeated attempts to discontinue the drug. All other organic factors were ruled out. The hypotension was proved to be secondary to sertraline by repeated rechallenges. After a variety of attempted treatments, the agent was discontinued successfully through an extended titration period. This report should guide clinicians in treating patients with a similar problem.

1-Naphthylamine↗
PubMedDate not supplied

Prospective validation of an optimal sparse plasma-sampling strategy for estimating ciprofloxacin pharmacokinetics.

Data obtained from 23 critically ill patients treated with intravenous ciprofloxacin in two clinical trials were used to validate prospectively a previously developed maximum a posteriori (MAP)-Bayesian estimator and optimal plasma-sampling strategy (OSS). Dosages ranged from 200 mg every 12 hours to 400 mg every 8 hours. Each patient had 8-16 samples taken, either as large gold standard sampling sets or as a mix of gold standard sets and OSSs. The MAP-Bayesian estimator used a two-compartment model and identified apparent volumes of distribution of the central and peripheral compartments, distributional clearance, and the slope and intercept of the relationship between creatinine clearance and total body clearance. Fit parameters were used to derive the apparent volume of distribution at steady state and the 24-hour area under the curve. All parameters derived from the OSS using the MAP-Bayesian estimates matched up almost identically to those obtained from modeling the gold standard sets. There was no systematic bias, and good precision was seen among all the parameters. These data demonstrate the usefulness and validity of the current OSS and MAP-Bayesian estimator, and provide further evidence of the utility of optimal sampling theory.

Adult↗
PubMedDate not supplied

Possible interaction between imipramine and butalbital.

A 44-year-old woman was admitted to the psychiatric unit for exacerbation of her depressive disorder. Blood concentrations of her antidepressant, imipramine, were within normal range and consistent with past concentrations. Her medical history was significant for a chronic headache disorder for which she was given a prescription containing butalbital on admission. The patient's depressive disorder was quickly controlled but relapsed 2 weeks later. Concentrations of imipramine showed a decrease of approximately 50%. Imipramine is metabolized in the liver by the cytochrome P-450 (CYP 1A2) system, and barbiturates are known inducers of this enzyme subset. To our knowledge, an interaction specifically between butalbital and imipramine has not been documented; however, these drugs are extensively prescribed and occasions may arise where they are given concurrently. We recommend repeat measurement of imipramine concentrations 1 week after the start of any butalbital-containing product or barbiturate, and dosage adjustments based on the results and on the patient's response to the change.

Adult↗
PubMedDate not supplied

Paradoxic excitation with diphenhydramine in an adult.

Although paradoxic excitation may rarely occur in children and adults with conventional dosages of antihistamines, few case reports have appeared in the literature. We cared for a 46-year-old patient who became extremely agitated after receiving a dose of intravenous diphenhydramine.

Adult↗