Use of saliva in therapeutic drug monitoring.

1977 ◽  
Vol 23 (2) ◽  
pp. 157-164 ◽  
Author(s):  
M G Horning ◽  
L Brown ◽  
J Nowlin ◽  
K Lertratanangkoon ◽  
P Kellaway ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Parent Drug ◽  
Free Fraction ◽  
Therapeutic Drug ◽  
Gas Chromatograph ◽  
Parotid Saliva ◽  
Paired Samples ◽  
Mixed Saliva

Abstract We measured the concentrations of phenobarbital, phenytoin, primidone, ethosuximide, antipyrine, and caffeine in paired samples of saliva and plasma by gas chromatograph-mass spectrometer-computer (GC/MS/COM) and enzyme immunoassay. Mixed saliva was collected for the antipyrine and caffeine studies, parotid saliva for the phenobarbital, primidone, ethosuximide and phenytoin studies. The saliva/plasma (S/P) ratios (by weight) obtained by GC/MS/COM were: phenobarbital, 0.31-0.37; phenytoin, 0.11; ethosuximide, 1.04; antipyrine, 0.83-0.95; caffeine, 0.55. The S/P ratio obtained by enzyme immunoassay were: phenobarbital, 0.32; phenytoin, 0.12; primidone, 0.85. The concentrations of phenytoin, primidone, ethosuximide and antipyrine in saliva correspond to the free fraction of the drug in plasma. When we analyzed samples containing phenobarbital or phenytoin (plasma or saliva) by both techniques, we found that the enzyme immunoassay values were generally higher than GC/MS/COM values, suggesting that the metabolites as well as the parent drug were measured in the immunoassay.

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment

2004 ◽  
Vol 42 (11) ◽  
Author(s):  
Herlinde Dumez ◽  
Gunther Guetens ◽  
Gert De Boeck ◽  
Martin S. Highley ◽  
Robert A. A. Maes ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Transport ◽  
Free Fraction ◽  
The Body ◽  
Cancer Drug ◽  
Therapeutic Drug ◽  
Anti Cancer ◽  
Plasma Compartment ◽  
Made In

AbstractTherapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.

HPLC-microparticle enzyme immunoassay specific for tacrolimus in whole blood of hepatic and renal transplant patients

1995 ◽  
Vol 41 (9) ◽  
pp. 1292-1296 ◽  
Author(s):  
I Firdaous ◽  
A Hassoun ◽  
J B Otte ◽  
R Reding ◽  
J P Squifflet ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Reference Method ◽  
Parent Drug ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Transplant Patients ◽  
Microparticle Enzyme Immunoassay ◽  
Renal Transplant Patients

Abstract Tacrolimus is a relatively new immunosuppressant used in organ transplantation to prevent graft rejection. However, its use is not devoid of side effects, making it important to maintain blood concentrations within therapeutic ranges. Several analytical methods are currently available for routine drug monitoring. However, these methods are based on use of the same monoclonal antibody, which also cross-reacts with some metabolites, resulting in overestimation of some blood concentrations. Even though this antibody appears appropriate for therapeutic drug monitoring, no reference method measures only the parent drug, mainly because of the poor absorptivity of tacrolimus in ultraviolet light. We have developed a method displaying an increased specificity towards the unchanged drug, using conventional equipment available in most clinical laboratories. After chromatographic separation of the blood extract, the tacrolimus fraction is analyzed by an automated microparticle enzyme immunoassay (MEIA) performed on the IMx analyzer (Abbott Labs.). This method is linear from 0 to 40 micrograms/L, yields CVs from 8.5% to 18.2%, and has a detection limit of 5 micrograms/L. Tacrolimus concentrations obtained by HPLC-MEIA in hepatic and renal transplant patients are from 47.5% to 18.8% lower than those obtained by MEIA, according to liver function tests and metabolite accumulation, even though no significant differences were observed between the methods for drug-free blood samples supplemented with known amounts of tacrolimus.

Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression

1994 ◽  
Vol 40 (12) ◽  
pp. 2247-2253 ◽  
Author(s):  
M Winkler ◽  
B Ringe ◽  
J Baumann ◽  
M Loss ◽  
K Wonigeit ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Concentrations ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Fk 506 ◽  
Blood Samples ◽  
The Matrix

Abstract By retrospective analysis of 13,000 blood samples obtained from 248 patients receiving FK 506 therapy, we compared the suitability of plasma with that of whole blood as the matrix for therapeutic drug monitoring of FK 506. The plasma concentrations did not correlate with the concentrations in whole blood (r = 0.56). In contrast to plasma samples (analyzed by enzyme immunoassay), FK 506 was detectable in all whole-blood samples (analyzed by enzyme immunoassay/microparticle enzyme immunoassay). The inter- and intraindividual variations of FK 506 measurements were greater in plasma than in whole blood. Moreover, plasma concentrations correlated only poorly with clinical events. There was a tendency to greater plasma concentrations being measured during episodes of toxicity, but no clear difference was evident between stable course and rejection. In whole-blood specimens, a correlation between reduced or increased FK 506 concentrations and rejection or toxicity, respectively, was observed. The discriminatory power of whole-blood values was greater for the differentiation between toxicity and stable course than between rejection and stable course. We therefore recommend whole blood rather than plasma as the matrix for therapeutic monitoring of FK 506 concentrations.

Poor Reliability of Therapeutic Drug Monitoring Data for Haloperidol and Bromperidol Using Enzyme Immunoassay

2003 ◽  
Vol 25 (6) ◽  
pp. 709-714 ◽  
Author(s):  
Norio Yasui-Furukori ◽  
Hanako Furukori ◽  
Manabu Saito ◽  
Yoshimasa Inoue ◽  
Sunao Kaneko ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Monitoring Data ◽  
Therapeutic Drug

Effects of Hematocrit Value on Microparticle Enzyme Immunoassay of Tacrolimus Concentration in Therapeutic Drug Monitoring

2005 ◽  
Vol 27 (1) ◽  
pp. 94-97 ◽  
Author(s):  
Takashi Tomita ◽  
Masato Homma ◽  
Kenji Yuzawa ◽  
Nobuhiro Ohkohchi ◽  
Tetsuo Hori ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Tacrolimus Concentration ◽  
Therapeutic Drug ◽  
Microparticle Enzyme Immunoassay

Dry-reagent strips used for determination of theophylline in serum.

1985 ◽  
Vol 31 (5) ◽  
pp. 737-740 ◽  
Author(s):  
P Rupchock ◽  
R Sommer ◽  
A Greenquist ◽  
R Tyhach ◽  
B Walter ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Calibration Line ◽  
Emergency Rooms ◽  
Serum Samples ◽  
Reagent Strips

Abstract A reagent strip for quantifying theophylline in serum or plasma has been developed for use with the Apoenzyme Reactivation Immunoassay System (ARIS) with the Ames Seralyzer reflectance photometer. The test takes 80 s and involves comparison with a two-point calibration line, which can validly be stored in the instrument for two weeks. Results for theophylline in clinical serum samples correlate well (r greater than 0.98) with results by liquid chromatography, fluoroimmunoassay, and enzyme immunoassay procedures. The within-run CV for four concentrations of controls ranged from 3.5 to 6%; the between-run CVs ranged from 3 to 5%. This assay for use in therapeutic drug monitoring is convenient, rapid, and simple, and thus is appropriate for use in emergency rooms, physician's offices, and small laboratories.

scholarly journals Monographs on drugs which are frequently analyzed in therapeutic drug monitoring/Arzneimittel-Monographien für Medikamente, die regelmäßig im Rahmen des Therapeutic Drug Monitorings analysiert werden

2012 ◽  
Vol 36 (2) ◽  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Clinical Chemistry ◽  
Parent Drug ◽  
Life Time ◽  
Antiretroviral Drugs ◽  
Blood Sampling ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
The Stability

AbstractIn addition to the monographs which have been published in the past 7 years by the working group “Drug Monitoring” of the Swiss Society of Clinical Chemistry (SSCC) [1–6], new monographs have been written. The data presented in these monographs provide an overview of the information which is important for the request and interpretation of the results. Therefore, laboratory health professionals and the receivers of the reports are the targeted readers. In this series, antiretroviral drugs are presented for which drug concentrations are regularly determined (protease inhibitors, non-nucleoside reverse transcriptase inhibitors). To date, no clear evidence has been established that therapeutic drug monitoring of these drugs increases the success of the antiretroviral therapy. Nevertheless, many cases have demonstrated that the therapy can be guided with much more confidence and with good success if the drug concentrations are determined, especially if the patient has a combination therapy with many pharmacokinetically interfering compounds. First, information is given about pharmacology and pharmacokinetics of these drugs, such as protein binding, metabolic pathways with specific enzymes involved, elimination half-life time, elimination route(s) of the parent drug, as well as therapeutic and toxic concentrations. Moreover, indications for therapeutic drug monitoring are listed with important preanalytical information (time point of blood sampling and time to steady state since beginning or after change of posology). Furthermore, the stability of the drug and its metabolite(s) after blood sampling are described. For readers with a specific interest, references to important publications are given. The number of monographs will be further enlarged. The updated files are presented on the homepage of the SSCC (www.sscc.ch). We hope that these monographs are helpful for the better handling of therapeutic drug monitoring and we are looking forward to receiving comments from the readers.

scholarly journals Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Julien Ollivier ◽  
Cédric Carrié ◽  
Nicolas d’Houdain ◽  
Sarah Djabarouti ◽  
Laurent Petit ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Creatinine Clearance ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Free Fraction ◽  
Compartment Model ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Dosing Regimens

ABSTRACT The objective of the present study was to determine whether augmented renal clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 9-month period, all critically ill patients treated with ceftriaxone were eligible. During the first 3 days of antimicrobial therapy, every patient underwent 24-h creatinine clearance (CLCR) measurements and therapeutic drug monitoring of unbound ceftriaxone. ARC was defined by a CLCR of ≥150 ml/min. Empirical underdosing was defined by a trough unbound ceftriaxone concentration under 2 mg/liter (percentage of the time that the concentration of the free fraction of drug remained greater than the MIC [fT>MIC], 100%). Monte Carlo simulation (MCS) was performed to determine the probability of target attainment (PTA) of different dosing regimens for various MICs and three groups of CLCR (<150, 150 to 200, and >200 ml/min). Twenty-one patients were included. The rate of empirical ceftriaxone underdosing was 62% (39/63). A CLCR of ≥150 ml/min was associated with empirical target underdosing with an odds ratio (OR) of 8.8 (95% confidence interval [CI] = 2.5 to 30.7; P < 0.01). Ceftriaxone PK concentrations were best described by a two-compartment model. CLCR was associated with unbound ceftriaxone clearance (P = 0.02). In the MCS, the proportion of patients who would have failed to achieve a 100% fT>MIC was significantly higher in ARC patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P < 0.01). A dose of 2 g twice a day was best suited to achieve a 100% fT>MIC. When targeting a 100% fT>MIC for the less susceptible pathogens, patients with a CLCR of ≥150 ml/min remained at risk of empirical ceftriaxone underdosing. These data emphasize the need for therapeutic drug monitoring in ARC patients.

scholarly journals Drug choice and therapeutic drug monitoring in the management of canine primary epilepsy : continuing education

1999 ◽  
Vol 70 (4) ◽  
Author(s):  
T. Vaughan ◽  
J.H. Taylor
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Drug Dosage ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Blood Concentrations ◽  
Paired Samples ◽  
Drug Choice ◽  
Optimal Drug ◽  
Pet Owner

Therapeutic drug monitoring is an underutilised resource in the management of canine primary epilepsy. Many of the anti-epileptic drugs, including phenobarbitone, have variable pharmacokinetic profiles in different dogs, with each individual animal showing variable rates of absorption, distribution, metabolism and excretion. This results in variable serumdrug concentrations with the same oral dose. Many clinicians interpret this situation as therapeutic failure and classify these patients as refractory to treatment. By measuring blood concentrations of drugs at appropriate times, it is possible to explain the efficacy or failure of treatment, and also to prevent serum concentrations from reaching toxic levels. By analysing paired samples, key pharmacokinetic parameters may be calculated for each patient and a profile for the disposition of the drug obtained. Individual optimal drug dosage can be calculated for each patient at little cost to the pet owner.

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