Inadequate plasma concentrations in some high-dose methadone maintenance patients

1987 ◽  
Vol 144 (10) ◽  
pp. 1349-1350 ◽  
Keyword(s):  
Methadone Maintenance ◽  
Plasma Concentrations ◽  
High Dose

Association study of genetic polymorphisms in GABRD with treatment response and dose in methadone maintenance treatment

2021 ◽  
Author(s):  
Xiaohu Xie ◽  
Jun Gu ◽  
Dingding Zhuang ◽  
Xiaoyu Chen ◽  
Yun Zhou ◽  
...  
Keyword(s):  
Treatment Response ◽  
Methadone Maintenance Treatment ◽  
Maintenance Treatment ◽  
Methadone Maintenance ◽  
Methadone Treatment ◽  
Heroin Addiction ◽  
High Dose ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Delta Subunit

Aim: This study determined if gene variants in the GABA receptor delta subunit ( GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. Materials & methods: A total of 286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose. Four (single nucleotide polymorphisms) SNPs (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped using the TaqMan SNP assay. Logistic regression was used to assess the genetic effects of the SNPs in MMT. Results: No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC at the four SNPs significantly differed between responders and nonresponders. Conclusion: The results indicated that GABRD variants may play a small role in modulating methadone treatment response.

Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment

2000 ◽  
Vol 61 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Chin B Eap ◽  
Michel Bourquin ◽  
Jean-Louis Martin ◽  
Jacques Spagnoli ◽  
Santino Livoti ◽  
...  
Keyword(s):  
Methadone Maintenance Treatment ◽  
Maintenance Treatment ◽  
Therapeutic Response ◽  
Methadone Maintenance ◽  
Plasma Concentrations

scholarly journals Clopidogrel Pharmacokinetics in Malaysian Population Groups: The Impact of Inter-Ethnic Variability

2018 ◽  
Vol 11 (3) ◽  
pp. 74 ◽  
Author(s):  
Zaril Zakaria ◽  
Alan Fong ◽  
Raj Badhan
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
High Dose ◽  
Population Groups ◽  
Adjunct Treatment ◽  
Malaysian Population ◽  
Significant Difference ◽  
Target Plasma Concentration ◽  
Ethnic Variability ◽  
The Impact

Malaysia is a multi-ethnic society whereby the impact of pharmacogenetic differences between ethnic groups may contribute significantly to variability in clinical therapy. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for up to 26% of all hospital deaths annually. Clopidogrel is used as an adjunct treatment in the secondary prevention of cardiovascular events. CYP2C19 plays an integral part in the metabolism of clopidogrel to the active metabolite clopi-H4. However, CYP2C19 genetic polymorphism, prominent in Malaysians, could influence target clopi-H4 plasma concentrations for clinical efficacy. This study addresses how inter-ethnicity variability within the Malaysian population impacts the attainment of clopi-H4 target plasma concentration under different CYP2C19 polymorphisms through pharmacokinetic (PK) modelling. We illustrated a statistically significant difference (P < 0.001) in the clopi-H4 Cmax between the extensive metabolisers (EM) and poor metabolisers (PM) phenotypes with either Malay or Malaysian Chinese population groups. Furthermore, the number of PM individuals with peak clopi-H4 concentrations below the minimum therapeutic level was partially recovered using a high-dose strategy (600 mg loading dose followed by a 150 mg maintenance dose), which resulted in an approximate 50% increase in subjects attaining the minimum clopi-H4 plasma concentration for a therapeutic effect.

scholarly journals Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 313 ◽  
Author(s):  
Rihong Guo ◽  
Fang Chen ◽  
Cheng Mei ◽  
Zicun Dai ◽  
Leyan Yan ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Reproductive Performance ◽  
Luteal Phase ◽  
Low Dose ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
High Dose ◽  
Reproductive Hormone ◽  
Conception Rates

This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.

Effects of acetylsalicylic acid on pulmonary vascular tone and membrane permeability in blood-perfused dog lung

1993 ◽  
Vol 75 (6) ◽  
pp. 2561-2569 ◽  
Author(s):  
K. Kambara ◽  
M. Arakawa ◽  
T. Segawa ◽  
F. Ando ◽  
M. Ohno ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Extravascular Lung Water ◽  
Vascular Tone ◽  
Low Dose ◽  
Pressor Response ◽  
Plasma Concentrations ◽  
High Dose ◽  
Constant Flow ◽  
Lung Water ◽  
Pulmonary Vasoconstriction

We studied the effects of acetylsalicylic acid (ASA) on pressor response, microvascular filtration coefficient (Kf), extravascular lung water, and plasma concentrations of cyclooxygenase- and 5-lipoxygenase-derived products in 21 blood-perfused dog lungs with constant flow. The lungs were perfused for 1 h with an intrapulmonary injection of saline as vehicle (n = 5), a low dose of ASA [136 +/- 25 (SD) micrograms/ml perfusate; n = 5], a high dose of ASA (1,006 +/- 278 micrograms/ml perfusate; n = 6), or alloxan (1,000 mg; n = 5). Alloxan significantly increased Kf and extravascular lung water, whereas neither the low nor high dose of ASA increased Kf or extravascular lung water. The ASA-induced increase in vascular resistance did not correlate with the extent of the decrease in perfusate 6-keto-prostaglandin F1 alpha or the ratio of perfusate 6-ketoprostaglandin F1 alpha to thromboxane B2. Moreover, ASA did not enhance the generation of perfusate leukotrienes B4, D4, or E4. We conclude that pulmonary microvascular permeability is unaltered by ASA and that neither the decrease in plasma prostacyclin nor the increase in plasma sulfidopeptide leukotrienes may account for ASA-induced pulmonary vasoconstriction.

Toremifene: pharmacologic and pharmacokinetic basis of reversing multidrug resistance.

1989 ◽  
Vol 7 (9) ◽  
pp. 1359-1364 ◽  
Author(s):  
M W DeGregorio ◽  
J M Ford ◽  
C C Benz ◽  
V J Wiebe
Keyword(s):  
Estrogen Receptor Status ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
High Dose ◽  
Human Breast ◽  
Human Breast Cell Line ◽  
Human Breast Cell ◽  
Mcf 7 ◽  
Resistant Cells

Triphenylethylene compounds, such as tamoxifen, have shown chemosensitizing activity independent of estrogen receptor status in doxorubicin-resistant cells. We examined the chemosensitizing activity of a new triphenylethylene, toremifene, and its major metabolites in a doxorubicin-resistant human breast cell line, MCF-7/DOX. In addition, we examined the chemosensitizing activity of unbound plasma toremifene and its metabolites isolated from patients treated with toremifene doses of 20 to 400 mg/d. MCF-7/DOX cells were exposed to ultrafiltrate plasma specimens in the absence and presence of doxorubicin. These latter studies were single-blinded. Toremifene and its major metabolites were capable of sensitizing multidrug-resistant cells to doxorubicin. The degree of chemosensitizing activity in vitro correlated with the plasma concentrations of toremifene and its metabolites (P less than .05). Plasma samples isolated from patients receiving high-dose toremifene (400 mg/d) had the greatest chemosensitizing activity. We present evidence that toremifene and its metabolites can sensitize resistant MCF-7/DOX cells to doxorubicin, that this effect is concentration-dependent, and that sensitizing activity can be detected at clinically achieved concentrations.

Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors.

1994 ◽  
Vol 12 (9) ◽  
pp. 1902-1909 ◽  
Author(s):  
D R Budman ◽  
L N Igwemezie ◽  
S Kaul ◽  
J Behr ◽  
S Lichtman ◽  
...  
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Performance Status ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Water Soluble ◽  
High Dose ◽  
Maximum Plasma ◽  
Rapid Infusion ◽  
Etoposide Phosphate

PURPOSE To determine the toxicities, maximum-tolerated dose (MTD), and pharmacology of etoposide phosphate, a water-soluble etoposide derivative, administered as a 5-minute intravenous infusion on a schedule of days 1, 3, and 5 repeated every 21 days. PATIENTS AND METHODS Thirty-six solid tumor patients with a mean age of 63 years, performance status of 0 to 1, WBC count > or = 4,000/microL, and platelet count > or = 100,000/microL, with normal hepatic and renal function were studied. Doses evaluated in etoposide equivalents were 50, 75, 100, 125, 150, 175, and 200 mg/m2/d. Etoposide in plasma and urine and etoposide phosphate in plasma were measured by high-performance liquid chromatography (HPLC). Eleven of 36 patients were treated with concentrated etoposide phosphate at 150 mg/m2/d. RESULTS Grade I/II nausea, vomiting, alopecia, and fatigue were common. Leukopenia (mainly neutropenia) occurred at doses greater than 75 mg/m2, with the nadir occurring between days 15 and 19 posttreatment. All effects were reversible. Hypotension, bronchospasm, and allergic reactions were not observed in the first 25 patients. The MTD due to leukopenia was determined to be between 175 and 200 mg/m2/d. In 11 patients treated with concentrated etoposide phosphate, no local phlebitis was noted, but two patients did develop allergic phenomena. The conversion of etoposide phosphate to etoposide was not saturated in the dosages studied. Etoposide phosphate had peak plasma concentrations at 5 minutes, with a terminal half-life (t1/2) of 7 minutes. Etoposide reached peak concentrations at 7 to 8 minutes, with a t1/2 of 6 to 9 hours. Both etoposide phosphate and etoposide demonstrated dose-related linear increases in maximum plasma concentration (Cmax) and area under the curve (AUC). CONCLUSION Etoposide phosphate displays excellent patient tolerance in conventional dosages when administered as a 5-minute intravenous bolus. The suggested phase II dose is 150 mg/m2 on days 1, 3, and 5. The ability to administer etoposide phosphate as a concentrated, rapid infusion may prove of value both in the outpatient clinic and in high-dose regimens.

Pharmacokinetic Evaluation of anti-HIV Drug Interactions: Effect of Zidovudine on 2′-3′-Dideoxyinosine Kinetics in Monkeys

1993 ◽  
Vol 4 (3) ◽  
pp. 155-159 ◽  
Author(s):  
M. Qian ◽  
A. R. Swagler ◽  
M. Mehta ◽  
C.T. Vishwanathan ◽  
J. M. Gallo
Keyword(s):  
Dose Group ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Combination Regimen ◽  
Time Profiles ◽  
Elimination Half ◽  
Constant Rate ◽  
Rate Infusion

The current investigation was conducted to determine if zidovudine (AZT) altered the pharmacokinetics of dideoxyinosine (ddl) in non-hurnan primates, an appropriate animal model for AZT and ddl pharmacokinetics in human. Each of nine animals received 20 mg kg−1 of ddl intravenously in the absence and presence of two different dosage regimens of AZT. For each combination regimen, AZT was administered as a combined i.v. bolus-constant rate infusion regimen for 30 min that produced AZT plasma concentrations of about 4 μg ml−1 in six animals (low dose group) and 11 μg ml−1 in three others (high dose group). Serial blood samples were collected, and pharmacokinetic parameters for ddl were calculated based on plasma ddl concentrations measured by HPLC techniques. The pharmacokinetics of ddl given alone in the first phase of the low ( n = 6) and high ( n = 6) dose AZT groups, resulted in a mean elimination half-life 1.54 and 1.9h, a mean total clearance of 0.62 and 0.731 h−1 kg−1, and a mean steady state volume of distribution of 1.02 and 0.891 kg−1, respectively. Following combined ddl and AZT administrations, in both the low and high dose AZT groups, plasma concentration-time profiles of ddl were similar for each monkey, and no statistical differences were observed in the pharmacokinetic parameters compared to those obtained when ddl was given alone. The fact that AZT does not alter the pharmacokinetics of ddl at the range of AZT dose studied provides a basis for rational dosage design for combined ddl and AZT treatments in HIV infection.

Vasoactive intestinal peptide and the stimulation of lactotroph growth by oestradiol in rats

1988 ◽  
Vol 116 (2) ◽  
pp. 259-265 ◽  
Author(s):  
R. A. Prysor-Jones ◽  
J. J. Silverlight ◽  
S. J. Kennedy ◽  
J. S. Jenkins
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Median Eminence ◽  
Direct Action ◽  
Plasma Concentrations ◽  
High Dose ◽  
Fischer 344 ◽  
Oestradiol Treatment ◽  
Pituitary Hyperplasia ◽  
Dopamine Content ◽  
Wet Weight

ABSTRACT Treatment with a high dose of oestradiol for 6 months caused hyperprolactinaemia and pituitary hyperplasia in female Wistar–Furth rats. Changes in the vasoactive intestinal peptide (VIP) and dopamine content of the hypothalamus and pituitary were also found. The hypothalamic dopamine concentration was only slightly reduced and, although the concentration of dopamine in the pituitary was less in treated animals, the total pituitary content was increased. The concentration of VIP in the pituitary was increased by oestradiol treatment but decreased in the non-median eminence hypothalamus. In the median eminence the VIP content was increased by oestradiol treatment and the amount present correlated positively and significantly with pituitary wet weight in animals treated with both oestradiol and fluphenazine. In Fischer 344 rats, oestradiol produced greater incremental changes in pituitary wet weight and plasma concentrations of prolactin than in Wistar controls and the increase in the pituitary concentration of VIP was five times greater. Although peptide turnover has not been measured, these results suggest that oestradiol, as well as having a direct action, stimulates pituitary lactotrophs by increasing pituitary concentrations of VIP. J. Endocr. (1988) 116, 259–265

High-Dose Ropivacaine Wound Infiltration for Pain Relief After Inguinal Hernia Repair

1998 ◽  
Vol 23 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Nils Pettersson ◽  
B-M Emanuelsson ◽  
Håkan Reventlid ◽  
Robert G. Hahn
Keyword(s):  
Pain Relief ◽  
Hernia Repair ◽  
Plasma Concentrations ◽  
High Dose ◽  
Hernia Surgery ◽  
Wound Infiltration ◽  
Surgeon General ◽  
Pain Scores ◽  
Control Pain ◽  
Pain At Rest

Background and ObjectivesEarly data on ropivacaine, a recently introduced local anesthetic, indicate a longer duration of skin analgesia than with bupivacaine, along with lower toxicity. The objective of this study was to evaluate ropivacaine 7.5 mg/mL for wound infiltration pain relief after hernia surgery, in higher doses than used before, in an open, nonrandomized design.MethodsTwenty otherwise healthy men underwent elective unilateral open hernia repair by the same surgeon. General anesthesia was used during surgery, and infiltration of the operating field with 300 mg (n = 10) or 375 mg (n = 10) ropivacaine, 7.5 mg/mL, was employed for postoperative pain relief. Any sign of an adverse event was recorded. Plasma concentrations of ropivacaine were monitored. Pain at rest and on mobilization was regularly assessed over 24 hours by a visual analog scale. Patients' ability to walk and void and the need for supplementary analgesics were recorded.ResultsNo serious adverse effects occurred. Plasma concentrations showed large variations but no toxic levels. No significant differences between the two groups were detected in pain scores which were low in both groups, at rest or on mobilization, or in the consumption of supplementary analgesics. At 4 hours, 19 patients were able to walk. Within 8 hours of surgery, all patients had passed urine without any problem. Wound healing was normal.ConclusionsInfiltration of ropivacaine 7.5 mg/mL during hernia surgery can be employed safely in doses of 300 mg and 375 mg to control pain after hernia surgery. The lower dose is recommended, since the higher one did not give any clinically relevant advantages.

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