Rational Therapeutic Drug Monitoring

Friedman, H.

doi:10.1001/jama.1986.03380160085025

Cited by 31 publications

(9 citation statements)

References 38 publications

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“…With the 2-g dose, significant increases in Cmax and AUC were noted in the aged population; the CL and CLR of cefoperazone were decreased. Recently, the influence of changes in serum protein and drug binding and their effects on total and free drug fractions have been considered (16). Higher free-drug levels have been demonstrated when highly protein-bound antibiotics were studied in elderly compared with younger patients (25).…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults

Meyers¹,

Mendelson²,

Deeter³

et al. 1987

Antimicrob Agents Chemother

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Two groups of 10 healthy ambulatory subjects, i.e., a group of 10 persons s30 years of age (mean age, 27.6 years) and a group of 10 persons .65 years of age (mean age, 70 years), were randomized in a single-trial crossover design to receive 1 and 2 g of cefoperazone with a 1-week washout between doses. The elderly subjects had both decreased estimated creatinine clearances and decreased albumin concentrations in serum. Cefoperazone concentrations in serum of elderly persons were significantly higher at each interval from 30 min to 6 h for the 2-g dose. Compared with that in younger persons, the total clearance in elderly subjects was significantly lower for both the 1-and 2-g doses, the renal clearance was significantly lower for the 2-g dose, and the area under the curve was significantly higher for the 2-g dose in the elderly persons. The half-life at i phase was higher in the elderly persons at both the 1-and 2-g doses but not significantly so. Changes in total clearance and area under the curve and higher levels in serum in the elderly persons suggest a longer duration of antimicrobial activity in this age group.The elderly (persons of >65 years of age) represent a significant and growing portion of the U.S. population, making up 12% of the total population in 1980 and estimated to increase to 17% in the year 2030 (38). Disproportionate percentages of health care expenditures (25 to 30%) (22) and prescription drugs dispensed (25%) (9) are generated by this segment of the population. In addition, the incidence of adverse reactions to drugs has been clearly demonstrated to be greater in the elderly (18).The newer extended-spectrum beta-lactam antimicrobial agents, with their potent antibacterial activity and relative lack of toxicity, are finding increased use as preferred agents for the treatment of elderly patients with infection. Their safety profile appears to be greater than that of the aminoglycosides that have been shown to be associated with increased rates of toxicity in the elderly (27).In view of age-associated altered drug absorption and disposition, decreased protein binding, renal clearance, hepatic drug metabolism (30, 33), and albumin levels (5, 26), and increased drug-drug interactions, it is possible that the pharmacokinetics of the new beta-lactam agents are altered as well. The pharmacokinetic properties of ceftriaxone (25), ceftazidime (23), and cefotaxime (20) in the elderly have shown differences compared with those in younger subjects.The pharmacokinetic properties of cefoperazone, a broadspectrum antipseudomonal cephalosporin (19), have been studied in healthy young volunteers. Excretion is via dual pathways; 15 to 37% is excreted in urine, with the remainder excreted by nonrenal mechanisms, predominantly the hepatobiliary system (12,17,36). Additional studies have been done in patients with impaired renal and hepatic functions (2,7,8,17) and in patients with renal dysfunction and active infection (32); altered pharmacokinetic parameters have been noted in these studies. We report here...

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Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults

Meyers¹,

Mendelson²,

Deeter³

et al. 1987

Antimicrob Agents Chemother

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“…The design of the study permitted for occupancy evaluation at 12-16 hours, that is, at trough plasma ziprasidone levels, which is known to provide more stable and less variable estimates across subjects (42,43). Although this design allowed us to determine plasma occupancy relationships for D 2 and 5-HT 2 receptors, it did not permit the inclusion of higher plasma levels in the regression analyses, which increases the risk of underestimating maximal receptor occupancy and ED 50 , particularly in the case of D 2 receptor occupancy.…”

Section: Discussionmentioning

confidence: 99%

A PET Study of Dopamine D₂ and Serotonin 5-HT₂ Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone

Mamo¹,

Kapur²,

Shammi³

et al. 2004

AJP

179

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These data affirm that ziprasidone is similar to other novel antipsychotics in having greater 5-HT(2) than D(2) receptor occupancy at therapeutic doses and suggest that the optimal effective dose of ziprasidone is closer to 120 mg/day than to the lower doses suggested by previous PET studies. The relatively high D(2) receptor occupancy, even at trough plasma levels, suggests that ziprasidone is more similar to risperidone and olanzapine in receptor occupancy profile than to clozapine and quetiapine. Since ziprasidone plasma levels show significant (more than twofold) variation within a single dose cycle, studies that are aimed at peak plasma levels (6 hours after the last dose) and that examine extrastriatal regions are required to fully characterize the in vivo occupancy profile of ziprasidone.

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“…The accumulating data indicate that TDM is still in need of careful evaluation for performance and cost-effectiveness. However, there is no doubt that TDM can produce lower toxicity, higher efficacy, and a lower-cost therapy than non-TDMguided therapy when it is performed according to the appropriate criteria and when the results are carefully interpreted (20,21).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Drug Monitoring in Turkey: Experiences From Istanbul

Yamantürk

Ozek

Sevgi

et al. 2000

Therapeutic Drug Monitoring

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Therapeutic drug monitoring (TDM) has assumed an important place in patient management in the last few decades. In this study, serum drug levels determined in 7759 specimens sent to the Department of Pharmacology and Clinical Pharmacology in 1994 and 1998 for TDM were retrospectively evaluated. Monitored drugs were carbamazepine, valproate, phenytoin, phenobarbital, digoxin, theophylline, and salicylate. The comparison of the results obtained for the relevant 2 years showed that there was a remarkable increase in the number of requests for TDM per year and in the rate of serum drug levels that were within therapeutic range. Serum antiepileptic drug level monitoring accounted for a major part of the data. Overall data suggest that the use of TDM in antiepileptic drugs is improving; conversely, digoxin and theophylline are still not being properly monitored. In this study, the results are discussed in the light of rational TDM criteria.

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Rational Therapeutic Drug Monitoring

Cited by 31 publications

References 38 publications

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults

A PET Study of Dopamine D₂ and Serotonin 5-HT₂ Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone

Therapeutic Drug Monitoring in Turkey: Experiences From Istanbul

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Rational Therapeutic Drug Monitoring

Cited by 31 publications

References 38 publications

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults

A PET Study of Dopamine D2 and Serotonin 5-HT2 Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone

Therapeutic Drug Monitoring in Turkey: Experiences From Istanbul

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A PET Study of Dopamine D₂ and Serotonin 5-HT₂ Receptor Occupancy in Patients With Schizophrenia Treated With Therapeutic Doses of Ziprasidone