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1. |
Phenytoin Excretion in Human Breast Milk and Plasma Levels in Nursed Infants |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 331-334
Bengt Steen,
Anders Rane,
Gudmar Lonnerholm,
Olle Falk,
Carl-Eric Elwin,
Folke Sjöqvist,
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摘要:
Phenytoin excretion into human breast milk was studied in six nursing women with epilepsy. The average ratio between the areas under the plasma (and milk) concentration versus time curves (AUC) was 0.13. There was a good (r = 0.97) correlation between the mean plasma and milk concentrations of phenytoin, and an even better relation (r = 0.99) between the AUC for phenytoin in plasma and the mean milk concentration. The ratio between unconjugated and conjugated 4-OH-phenytoin (the main metabolite) in plasma was 0.08–0.09. The corresponding ratio in milk was considerably higher. The present data do not argue against breast feeding during phenytoin therapy, not even when weighed against the potential risks for toxicity of the parent compound. Only two of six infants had a measurable, yet very low plasma concentration of phenytoin. The calculated body weight-related doses of phenytoin secreted into milk will be less than 5% of the dose to infants and small children.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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2. |
Saliva Concentrations of Lidocaine and Its Metabolites in Man |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 335-340
A. Barchowsky,
W. Stargel,
D. Shand,
P. Routledge,
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摘要:
The plasma concentrations of lidocaine and its two major active metabolites, monoethylglycylxylidide (MEGX) and glycylxylidide (GX), were measured in simultaneously mixed saliva and plasma samples from 16 patients who had received the drug intravenously for at least 12 h. The concentrations of each compound in saliva tended to be greater than those in the corresponding plasma sample, so that the mean saliva-to-plasma ratio for lidocaine was 2.9 (median, 2.65); for GX, 4.7 (median 2.2); and for MEGX, 7.0 (median, 6.4). There was a statistically significant, although rather weak, relationship between the saliva and the total plasma lidocaine concentrations (r = 0.700; n = 16; p < 0.01) and between the saliva and the free (unbound) plasma lidocaine concentrations (r = 0.509; n = 16; p < 0.05). When the latter was corrected for the effect of pH, the relationship was significant but still weak (Spearman's P = 0.619; p < 0.05). It appears that mixed salivary lidocaine concentrations are a relatively poor guide to free drug concentrations at steady state, even if correction is made for pH changes. Other rapid and convenient methods of estimating free plasma lidocaine concentrations are clearly needed.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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3. |
Determination of Unbound Valproic Acid Concentration in Plasma by Equilibrium Dialysis and Gas—Liquid ChromatographyMethodological Aspects and Observations in Epileptic Patients |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 341-352
Roberto Riva,
Fiorenzo Albani,
Agostino Baruzzi,
Ianna Galvani,
Emilio Perucca,
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摘要:
An equilibrium dialysis technique for the separation of the free (unbound) concentration of valproic acid (VPA) in plasma is described together with a sensitive gas chromatographic assay for the quantitative determination of the drug in the dialysate. The overall coefficient of variation of the method was below 10%. By using a high permeability membrane, equilibration of the drug between the plasma and the buffer compartments was obtained after about 45 min at 37°C. With this dialysis time, dilutional changes in the plasma compartment were negligible and there was no significant change in the plasma-free fatty acid (FFA) concentration. No passage of protein into the buffer solution was detected. When dialysis was prolonged for up to 4 h, a significant elevation in plasma FFA (with a corresponding rise in free VPA fraction) was observed. Storage of plasma samples at temperatures ranging from 4 to 37°C for 8 h or longer before dialysis also resulted in an increased value of free VPA fraction and FFA concentration. The two effects were significantly correlated. The free fraction of VPA was found to increase with increasing total plasma concentration. This effect was observed both in vitro and in vivo in the plasma of 91 patients receiving chronic VPA therapy. The methodological problems of using equilibrium dialysis techniques for determining the free fraction of VPA are highlighted.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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4. |
Phenytoin‐Allopurinol InteractionMichaelis‐Menten Kinetic Parameters of Phenytoin With and Without Allopurinol in a Child with Lesch‐Nyhan Syndrome |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 353-358
Kenji Yokochi,
Akiko Yokochi,
Kan Chiba,
Takashi Ishizaki,
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摘要:
We analyzed Michaelis—Menten pharmacokinetic parameters of phenytoin with and without the coadministration of allopurinol (150 and 200 mg/day) in a child with Lesch-Nyhan syndrome. The Vmaxand Kmwere estimated from at least two different sets of serum concentration-dosage data of phenytoin. The Vmaxvalues (mg/kg/day) were 16.1 without allopurinol, and 12.4 and 10.9 with allopurinol (150 and 200 mg/day), respectively, whereas those for Kmremained relatively constant (3.9 to 4.9 μg/kgml). Our results suggest that allopurinol is a drug that inhibits the hepatic metabolism of phenytoin.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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5. |
Determination of Mianserin in Human Plasma by Gas—Liquid Chromatography |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 359-364
Gérard Lachâtre,
Georges Nicot,
Louis Merle,
Jean Valette,
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摘要:
The authors describe a method for the plasma determination of mianserin by gas-liquid chromatography (GLC), using cyproheptadine as an internal standard. After extraction from 2 ml of plasma by a hexane:isoamyl alcohol (99:1, vol/vol) mixture and its purification by reextraction, the mianserin is determined by GLC, using a glass column packed with 3% OV1 on Gas-Chrom Q, and a nitrogen-sensitive detector. Since the between-day coefficient of variation (n = 15) is less than 8%, this technique appears to be sufficiently reproducible for routine determination in therapeutic concentrations (detection limit with accuracy = 2.5 μg/kgL). As an example, the authors describe the time variations of the plasma concentration of mianserin after a first-dose ingestion of 30 mg. Preliminary studies of kinetic parameters are determined in 11 adult patients following a single oral dose (30 mg of mianserin).
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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6. |
A Sensitive Gas Chromatographic Assay for Amitriptyline and Nortriptyline in Plasma |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 365-370
Petter-Arnt Hals,
Tor-Ivar Lundgren,
Jarle Aarbakke,
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摘要:
A method for the quantitative determination of the tricyclic antidepressant drug amitriptyline (AT) and its active major metabolite, nortriptyline (NT), in plasma is described. The method involves a three-step extraction procedure, no derivatization, and a rapid run on a gas—liquid chromatograph equipped with a nitrogen detector. The standard curves were linear in the range of 25–1,000 ng/ml. The lower detection limit was 2–5 ng/ml for both drugs. The method is specific for AT and NT, with a recovery of AT and NT of 68 and 71%, respectively. The precision of the method, expressed as the coefficient of variation, was 10.7% for AT and 12.9% for NT within 25—1,000 ng/ml. The method has proven to be suitable for monitoring plasma levels of AT and NT in patients, and in animals during experimental studies on pharmacokinetics after therapeutic and toxic doses of NT.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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7. |
Analysis of Methotrexate and 7‐Hydroxymethotrexate by High‐Performance Liquid Chromatography and Preliminary Clinical Studies |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 371-380
Christine Collier,
Stuart MacLeod,
Steven Soldin,
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摘要:
The simultaneous analysis of methotrexate (MTX) and its putatively nephrotoxic metabolite, 7-hydroxymethotrexate (70H-MTX), by high-performance liquid chromatography (HPLC) and ultraviolet spectrophotometric detection is described. Serum extraction employs SEP-PAK® C-18 cartridges. Recovery ranges from 78.3 to 84.9% for MTX and 67.6 to 76.1% for 70H-MTX. Between-day precision studies of serum (controls), containing 2.76 μM MTX and 4.40 μM 70H-MTX, yielded coefficients of variation of 8.6 and 8.9%, respectively. Reconstitution of the dried residue in 5 mM HC1 increases the retention times of 70H-MTX and MTX, thereby enhancing their separation from extraneous serum peaks. A comparison of MTX levels determined by HPLC and a competitive protein binding assay yielded consistently lower results by HPLC. However, in comparing HPLC to EMIT®, two relationships were observed: below 100 μM MTX the methods were in agreement, whereas above 100 μM MTX HPLC again provided lower values. Preliminary pharmacokinetic studies on two patients with osteogenic sarcoma are reported. After receiving 218.2 mg/kg and 148.5 mg/kg MTX in a 6-h infusion, their β half-lives for MTX were 2.6 and 2.0 h, while their γ half-lives were 26.2 and 42.9 h, respectively. The 7OH-MTX β half-lives were 5.8 and 4.0 h, and the γ half-lives were 10.2 and 15.8 h. Plasma concentration ratios of 7OH-MTX to MTX were 28.5 and 18.1 at 24 h after MTX infusion. 7OH-MTX was detected in the 15-min sample after the beginning of the MTX infusion.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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8. |
A Sensitive Assay Method of Furosemide in Plasma and Urine by High‐Performance Liquid Chromotography |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 381-384
Walter Snedden,
Jagdish Sharma,
Peter Fernandez,
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摘要:
A sensitive assay method of furosemide in plasma and urine by high-performance liquid chromatography (HPLC) is described. The minimum measurable concentrations of furosemide in plasma and urine were 0.2 and 5.0 μg/kgml, respectively; whereas the coefficients of variation of furosemide levels were found to be 7.8% for plasma and 2.0% for urine. These are within the acceptably low limits. Hence, the present method of furosemide is sensitive, reproducible, and accurate for therapeutic drug monitoring. The significance of this HPLC assay method is discussed.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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9. |
High‐Performance Liquid Chromatographic Measurement of Amiodarone and Its Desethyl MetaboliteMethodology and Preliminary Observations |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 385-388
G. Storey,
D. Holt,
Phyllis Holt,
P. Curry,
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摘要:
A high-performance liquid chromatographic technique is described for the measurement of amiodarone and its desethyl metabolite in plasma. Preliminary observations are presented on the concentrations of metabolite found during the early stages of chronic amiodarone therapy. A case history is outlined in which noncompliance during treatment with amiodarone was confirmed by measurement of the ratio of desethylamiodarone to amiodarone concentrations.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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10. |
A High Pressure Liquid Chromatographic Procedure for Monitoring1-(2‐Chloroethyl)-3-(4-trans-methylcyclohexyl)-1‐nitrosourea Levels in Body Fluids |
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Therapeutic Drug Monitoring,
Volume 4,
Issue 4,
1982,
Page 389-396
B. Caddy,
O. Idowu,
J. Stuart,
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摘要:
A reverse phase high pressure liquid chromatographic method has been developed for the analysis of l-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-l-nitrosourea (methyl-CCNU) levels present in body fluids. A value obtained for the plasma half-life for a single patient indicates that this may be larger than hitherto expected.
ISSN:0163-4356
出版商:OVID
年代:1982
数据来源: OVID
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