Transporters and Their Impact on Drug Disposition

2005 ◽  
Vol 39 (6) ◽  
pp. 1097-1108 ◽  
Author(s):  
Paul M Beringer ◽  
Richard L Slaughter
Keyword(s):  
Patient Outcomes ◽  
Drug Disposition ◽  
Data Extraction ◽  
The Body ◽  
Pertinent Literature ◽  
Data Synthesis ◽  
Medline Search ◽  
Manual Search ◽  
Study Selection ◽  
The Impact

OBJECTIVE: To review the recent advances in knowledge about human transporters and their effect on drug disposition. DATA SOURCES: A MEDLINE search (1996–March 2005) was performed to identify pertinent literature on human transporters and their impact on drug disposition. Additional articles were identified from a manual search of the references of retrieved articles. STUDY SELECTION AND DATA EXTRACTION: Based on the identified studies, data were extracted on the impact of transporters on drug absorption, distribution, and elimination. DATA SYNTHESIS: The pharmacokinetic disposition of drugs is known to be influenced by metabolic enzymes, kidney function, and transporters. Recent research on human transporters has greatly advanced our understanding of their diversity and importance in drug disposition. In particular, members of the multidrug resistance family of transporters (MDR, MRP) are present in organs and tissues throughout the body and are known to significantly affect the absorption, distribution, and elimination of commonly prescribed drugs. A growing number of studies now demonstrate that alterations in transporter function as a result of drug interactions or genetic polymorphisms may explain a significant portion of the variability in treatment response for certain drugs. CONCLUSIONS: Human transporters contribute significantly to the pharmacokinetic disposition of drugs. Knowledge of substrates, inducers, and inhibitors of these transporters is necessary to ensure optimal patient outcomes.

Isoniazid-Associated Psychosis: Case Report and Review of the Literature

1993 ◽  
Vol 27 (2) ◽  
pp. 167-170 ◽  
Author(s):  
Karen A. Pallone ◽  
Morton P. Goldman ◽  
Matthew A. Fuller
Keyword(s):  
Case Report ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Data Sources ◽  
Review Of The Literature ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Language Literature

Objective To describe a case of isoniazid-associated psychosis and review the incidence of this adverse effect. Data Sources Information about the patient was obtained from the medical chart. A MEDLINE search of the English-language literature published from 1950 to 1992 was conducted and Index Medicus was manually searched for current information. Study Selection All case reports describing isoniazid-associated psychosis were reviewed. Data Extraction Studies were evaluated for the use of isoniazid, symptoms of psychosis, onset of symptoms, and dosage of isoniazid. Data Synthesis The case report is compared with others reported in the literature. The incidence of isoniazid-associated psychosis is rare. Conclusions The mechanism of isoniazid-associated psychosis is uncertain. It appears that isoniazid was associated with the psychosis evident in our patient and in the cases reviewed.

Dexrazoxane: A New Cardioprotective Agent

1998 ◽  
Vol 14 (5) ◽  
pp. 182-190 ◽  
Author(s):  
Beverly D Abbott ◽  
Cindy M Ippoliti
Keyword(s):  
Supportive Care ◽  
English Language ◽  
Bolus Dose ◽  
Cardiac Tissue ◽  
Data Extraction ◽  
Data Synthesis ◽  
Medline Search ◽  
Search Terms ◽  
Study Selection ◽  
Clinically Significant

Objective: To review the literature discussing the use of dexrazoxane (e.g., Zinecard, ICRF-187) to prevent doxorubicin-induced cardiotoxicity. Data Sources: Pertinent English-language reports of studies in humans were retrieved from a MEDLINE search (January 1980-January 1997); search terms included chelating agents, razoxane, dexrazoxane, Zinecard, ICRF-187, ADR-529, and ICRF-159. Study Selection: Representative articles discussing the chemistry, pharmacology, pharmacokinetics, dosing, and administration of dexrazoxane and those discussing clinical trials were selected. Data Extraction: Data were extracted and analyzed if the information was relevant and consistent. Studies were selected for review in the text on the basis of study design and clinical end points. Data Synthesis: Dexrazoxane is a chemoprotective agent developed to prevent cardiac tissue toxicity. Dexrazoxane exerts a cardioprotective effect with some clinically significant toxicities; it may also interfere with the antitumor activity of doxorubicin. Until there are sufficient data to support its use in first-line supportive care therapy, dexrazoxane should be reserved for use in patients responding to doxorubicin-based chemotherapy but who have risk factors for cardiac toxicity or have received a cumulative doxorubicin bolus dose of 300 mg/m2. Conclusions: The management of doxorubicin-induced cardiotoxicity has led to the development of supportive care drugs that specifically counteract the dose-limiting toxicities. Dexrazoxane may not completely eliminate the concern about doxorubicin-induced cardiotoxicity, but it may open new avenues for continuing doxorubicin-based chemotherapy.

Changing Perspectives of Stress Gastritis Prophylaxis

1994 ◽  
Vol 28 (9) ◽  
pp. 1073-1085 ◽  
Author(s):  
Maureen A. Smythe ◽  
Barbara J. Zarowitz
Keyword(s):  
Risk Factors ◽  
Critically Ill ◽  
Data Extraction ◽  
Care Patient ◽  
Receptor Antagonists ◽  
Data Synthesis ◽  
Medline Search ◽  
Prophylactic Agent ◽  
Study Selection ◽  
Meta Analyses

OBJECTIVE: To present recent advances in stress gastritis prophylaxis in the critically ill and review considerations in selection of a prophylactic agent. DATA SOURCES: Information was obtained from MEDLINE search, reference lists from articles identified in search, and from review articles. STUDY SELECTION: Emphasis was placed on controlled trials conducted within the last 5 years. DATA EXTRACTION: All literature was assessed for methodology, results, and conclusions. Results of prospective, randomized trials, and meta-analyses are summarized. DATA SYNTHESIS: Histamine2-receptor antagonists, antacids, and sucralfate appear equally effective in preventing stress gastritis in the critically ill. A definitive cause–effect relationship between histamine2-receptor antagonists and increased incidence of nosocomial pneumonia has not yet been established. The indications for using a prophylactic agent and consideration in selecting an agent should include an evaluation of the following: Risk factors for gastritis including the type of intensive care patient, comparative efficacy, adverse effects, drug interactions, cost, and ease of administration. The least expensive, safest agent requiring minimal monitoring is sucralfate. Prevention of stress gastritis has never been shown to reduce morbidity or mortality significantly. CONCLUSIONS: Controversies still exist regarding the need to provide prophylaxis, the choice of an agent, and the relative importance of previously identified risk factors. Further well-designed studies are needed before consensus can be reached.

A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock

2018 ◽  
Vol 52 (9) ◽  
pp. 920-927 ◽  
Author(s):  
Brittany D. Bissell ◽  
Kelsey Browder ◽  
Matt McKenzie ◽  
Alexander H. Flannery
Keyword(s):  
Angiotensin Ii ◽  
Data Extraction ◽  
Peptide Hormone ◽  
Vasodilatory Shock ◽  
Vasoactive Agent ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Significant Difference ◽  
Distributive Shock

Objective: To review and summarize data on angiotensin II (AT-II), approved by the Food and Drug Administration (FDA) in December 2017 to increase blood pressure in adults with septic or other distributive shock. Data Sources: A PubMed/MEDLINE search was conducted using the following terms: (angiotensin ii OR angiotensin 2) AND (shock) from 1966 to February 2018. Study Selection and Data Extraction: A total of 691 citations were reviewed with only relevant clinical data extracted. Data Synthesis: AT-II is a peptide hormone with a multitude of physiological effects—namely, vasoconstriction of venous and arterial smooth muscle. The priority approval granted by the FDA was secondary to a phase 3 study of patients receiving at least 0.2 µg/kg/min of norepinephrine or equivalent for vasodilatory shock. Compared with placebo, AT-II had a significantly higher rate of response, defined as a mean arterial pressure of 75 mm Hg or an increase of 10 mm Hg. No significant difference was found in death by day 28. Conclusions: AT-II is a newly available vasoactive agent with a novel mechanism for the treatment of distributive shock. Further research is needed to define its exact role in therapy of shock states, identify patients most likely to benefit, and further study its safety profile in critical illness.

Rifaximin: A New Treatment for Travelers' Diarrhea

2005 ◽  
Vol 39 (2) ◽  
pp. 284-289 ◽  
Author(s):  
Amy L Pakyz
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
English Language ◽  
Data Extraction ◽  
Cross Resistance ◽  
Double Blind ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
New Treatment

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions and precautions, and dosing recommendations of rifaximin, a new nonabsorbed antimicrobial agent for travelers' diarrhea. DATA SOURCES: A MEDLINE search (1966–July 2004) was conducted to extract human and animal research data in the English language on rifaximin. STUDY SELECTION AND DATA EXTRACTION: Randomized, double-blind, placebo-controlled trials were reviewed and included to evaluate the efficacy of rifaximin in the treatment of travelers' diarrhea. DATA SYNTHESIS: Rifaximin is approved for the treatment of travelers' diarrhea in patients ≥12 years of age with diarrhea caused by noninvasive strains of Escherichia coli. Rifaximin was superior to placebo and trimethoprim/sulfamethoxazole and equivalent to ciprofloxacin in the primary clinical endpoint of the time to the last unformed stool passed. CONCLUSIONS: Rifaximin is a viable alternative to ciprofloxacin for the treatment of travelers' diarrhea. As rifaximin is not systemically absorbed, it offers the advantage of leading to the development of less resistance compared with systemically absorbed antibiotics, in addition to fewer systemic adverse effects and drug interactions. However, the potential for cross-resistance between rifaximin and rifampin, as well as with other classes of antibiotics, is of concern and needs to be elucidated.

Loss of Seizure Control Associated with Generic Substitution of Carbamazepine

1992 ◽  
Vol 26 (6) ◽  
pp. 775-777 ◽  
Author(s):  
Timothy E. Welty ◽  
Patricia R. Pickering ◽  
Bradford C. Hale ◽  
Richard Arazi
Keyword(s):  
Generic Substitution ◽  
Seizure Control ◽  
Data Extraction ◽  
Pertinent Literature ◽  
Data Synthesis ◽  
Actual Clinical Practice ◽  
First Case ◽  
The Impact ◽  
To Receive ◽  
Carbamazepine Concentration

OBJECTIVE: We report two cases of lost seizure control associated with the generic substitution of carbamazepine, review pertinent literature, and discuss the impact of this substitution on patient care. DATA SOURCES: Case studies, abstracts, and research publications identified in MEDLINE and bibliographic review. DATA EXTRACTION: One author reviewed cases supplied by the other authors and abstracted information from published literature sources. DATA SYNTHESIS: The first case describes a 15-year-old boy who received valproic acid and carbamazepine for partial seizures. A change in government program policies caused him to receive generic carbamazepine. This resulted in loss of seizure control and a decrease in his serum carbamazepine concentration from 12.4 to 6.7 μg/mL. When his carbamazepine concentration returned to previous levels, seizure control was not reestablished. A second case involves a 21-year-old woman who substituted generic carbamazepine because of financial problems. After being seizure-free for at least five years on phenobarbital and carbamazepine, she experienced seizures related to the product change. Her carbamazepine concentration decreased from 11.8 to 8.5 μg/mL; she also became pregnant at that time. Seizure control was not reestablished. At least three other studies do not support these observations, but the tightly controlled conditions in these studies may not have simulated actual clinical practice. CONCLUSIONS: When generic substitution of carbamazepine is required, serum concentrations should be carefully monitored. The extra care required may negate the financial advantages of the substitution.

Impact on Decisions to Start or Continue Medicines of Providing Information to Patients about Possible Benefits and/or Harms

2011 ◽  
Vol 31 (5) ◽  
pp. 767-777 ◽  
Author(s):  
Rachel A. Crockett ◽  
Stephen Sutton ◽  
Fiona M. Walter ◽  
Megan Clinch ◽  
Theresa M. Marteau ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Data Extraction ◽  
Decisional Conflict ◽  
Mean Difference ◽  
Data Sources ◽  
Inclusion Criteria ◽  
Data Synthesis ◽  
Study Selection ◽  
The Impact

Background. The impact of providing information about medicines to patients on decisions about starting or continuing them is unknown. Purpose. To estimate the impact on decisions to start or continue medicines, of providing information to patients about possible benefits and/or harms. Data Sources. Electronic searches from 1980 to October 2010; reference and citation searches of included studies. Study Selection. Two investigators assessed studies' eligibility against inclusion criteria: randomized or pseudorandomized trials; participants older than 16 years and deciding for themselves; one group received information about possible benefits and/or harms of a potentially beneficial medicine, compared with another who did not; d) a measure of decision about starting or continuing a medicine. Data Extraction. One investigator extracted all data, checked by a second. Data Synthesis. Eight studies were included, covering a range of medicines. There was no consistent impact of interventions on decisions about whether to start or continue medicines (pooled odds ratio 1.08; 95% confidence interval [CI], 0.69–1.70; P = 0.74). Among those who received more information, knowledge was increased (pooled mean difference 8.47; 95% CI 2.17–14.77; P = 0.008), and decisional conflict was reduced (pooled mean difference -0.15; 95% CI -0.24 to -0.06; P = .001). Limitations. A small number of studies across different clinical contexts, of uncertain heterogeneity, were included. Conclusions. Providing information to patients about possible benefits and/or harms has no consistent effect on the number who decide to start or continue medicines, although it increases patients' knowledge and reduces their decisional conflict.

Drug-Induced Alterations in Serum Creatinine Concentrations

1993 ◽  
Vol 27 (5) ◽  
pp. 622-633 ◽  
Author(s):  
Edward A. Hartshorn ◽  
Murray P. Ducharme ◽  
Maureen Smythe ◽  
Greg Strohs
Keyword(s):  
Serum Creatinine ◽  
Reference Lists ◽  
Data Extraction ◽  
Alternative Methods ◽  
Drug Induced ◽  
Data Synthesis ◽  
Comprehensive Review ◽  
Medline Search ◽  
Study Selection ◽  
Assay Interference

OBJECTIVE: To provide a comprehensive review of drug-induced alterations in serum creatinine concentrations (SCrs). DATA SOURCES: Information was obtained from a MEDLINE search, reference lists from articles identified in the search, review articles, and abstracts. STUDY SELECTION: Emphasis was placed on clinical studies of direct relevance to clinical practitioners. DATA EXTRACTION: Literature was assessed for its methodology, results, discussion, and conclusion. DATA SYNTHESIS: Two analytical systems to assay SCr are commonly employed in clinical practice—the Jaffé-based and enzymatic methods. Several drugs have been reported to interfere with SCr results obtained with both analytical systems by producing assay interference. In addition, trimethoprim, cimetidine, and salicylates produce elevations in the SCr by altering the normal elimination pathways of creatinine. Phenacemide has been reported to increase creatinine elimination, but the mechanism of this effect is unknown. CONCLUSIONS: Pharmacists should recognize the clinical significance of drug-induced interference with SCr and propose alternative methods of determining concentrations in selected patients.

Felbamate

1993 ◽  
Vol 27 (9) ◽  
pp. 1073-1081 ◽  
Author(s):  
Nina M. Graves
Keyword(s):  
Adverse Effects ◽  
Data Extraction ◽  
Pharmacokinetic Studies ◽  
Newly Diagnosed ◽  
Pertinent Literature ◽  
Complex Partial Seizures ◽  
Data Synthesis ◽  
Study Selection ◽  
Antiepileptic Medication ◽  
Subsequent Literature

OBJECTIVE: To provide an up-to-date review of the current literature on felbamate (FBM) and its use as an antiepileptic medication (AEM). DATA SOURCES: All published literature (manuscripts and abstracts) on FBM was reviewed. The initial bibliography (up to September 1992) was provided by the manufacturer (Carter-Wallace Laboratories); subsequent literature was obtained from American Epilepsy Society presentations in December 1992 and manuscripts published up to January 1993. STUDY SELECTION/DATA EXTRACTION: All pertinent literature was reviewed. Information from the publications was abstracted and organized by the author. DATA SYNTHESIS: FBM is effective in complex partial seizures either as monotherapy or as an adjunct in patients receiving other AEMs. In addition, it has shown efficacy in some seizures associated with the Lennox-Gastaut syndrome. Adverse effects appear to be mild. When FBM is given as monotherapy, the primary adverse effects are insomnia and weight loss. Patients receiving multiple AEMs may have increased adverse effects. CONCLUSIONS: FBM appears to be an effective new AEM. Additional studies as to its role in newly diagnosed and pregnant patients are needed. Pharmacokinetic studies in children, patients with renal failure, and patients on nonepilepsy drugs also are needed.

Ambulatory Care Pharmacy Services: The Incomplete Agenda

1992 ◽  
Vol 26 (5) ◽  
pp. 701-708 ◽  
Author(s):  
Barry L. Carter ◽  
Dennis K. Helling
Keyword(s):  
Ambulatory Care ◽  
Patient Outcomes ◽  
Clinical Pharmacy ◽  
English Language ◽  
Data Extraction ◽  
Pharmacy Services ◽  
Clinical Pharmacy Services ◽  
Standards Of Practice ◽  
Study Selection ◽  
The Impact

OBJECTIVE: To review studies that document the impact of clinical pharmacy services in ambulatory care settings and to propose standards of practice and resource allocation needs in ambulatory care. DATA SOURCES: English-language literature from 1970 through 1991 was reviewed and the representative literature is described. STUDY SELECTION: Studies were selected that examined the impact of clinical pharmacy services on patient outcomes and costs. Studies that evaluated pharmacist consultations by blind peer-review panels were also evaluated. DATA EXTRACTION: Trials were assessed based on their methodologies and ability to assess the value of clinical pharmacy services on patient outcomes. DATA SYNTHESIS: Numerous studies from the past 20 years are described illustrating the impact that ambulatory care pharmacy practitioners have made on patient care. These studies demonstrate that clinical pharmacists in ambulatory care not only serve as consultants on pharmacotherapy issues, but also can improve the quality of care for individual patients. CONCLUSIONS: Based on the studies cited and the needs of ambulatory patients, this article highlights the authors' views on what the standards of practice should be for ambulatory care practitioners and where resources should be allocated as ambulatory programs are expanded.

Sign in / Sign up

Export Citation Format

Share Document