PK/TK Analysis of Xenobiotics Absorbed via an Extravascular Route of Administration (Oral Administration)

2015 ◽  
pp. 382-417
Keyword(s):  
Oral Administration ◽  
Route Of Administration

scholarly journals Anticoagulation Treatment in Cancer-Associated Venous Thromboembolism: Assessment of Patient Preferences Using a Discrete Choice Experiment (COSIMO Study)

2020 ◽  
Author(s):  
Nils Picker ◽  
Agnes Y. Lee ◽  
Alexander T. Cohen ◽  
Anthony Maraveyas ◽  
Jan Beyer-Westendorf ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Oral Administration ◽  
Discrete Choice Experiment ◽  
Discrete Choice ◽  
Patient Preferences ◽  
Choice Experiment ◽  
Oral Anticoagulants ◽  
Daily Intake ◽  
Anticoagulation Therapy ◽  
Route Of Administration

Abstract Introduction Clinical guidelines recommend anticoagulation therapy for the treatment of cancer-associated venous thromboembolism (VTE), but little is known about preferences. Therefore, the objective of this discrete choice experiment (DCE) was to elucidate patient preferences regarding anticoagulation convenience attributes. Methods Adult patients with cancer-associated VTE who switched to direct oral anticoagulants were included in a single-arm study (COSIMO). Patients were asked to decide between hypothetical treatment options based on a combination of the following attributes: route of administration (injection/tablet), frequency of intake (once/twice daily), need for regular controls of the international normalized ratio (INR) at least every 3 to 4 weeks (yes/no), interactions with food/alcohol (yes/no), and distance to treating physician (1 vs. 20 km) as an additional neutral attribute. DCE data were collected by structured telephone interviews and analyzed based on a conditional logit regression. Results Overall, 163 patients (mean age 63.7 years, 49.1% female) were included. They strongly preferred oral administration compared with self-injections (importance of this attribute for overall treatment decisions: 73.8%), and a treatment without dietary restrictions (11.8%). Even if these attributes were less important (7.2% and 6.5%, respectively), patients indicated a preference for a shorter distance to the treating physician and once-daily dosing compared with twice-daily intake. “Need for regular controls of INR at least every 3 to 4 weeks” showed no significant impact on the treatment decision (0.7%). Conclusion This study showed that treatment-related decision making in cancer-associated VTE, assuming comparable effectiveness and safety of anticoagulant treatments, is predominantly driven by “route of administration,” with patients strongly preferring oral administration.

scholarly journals Assessment of the Reinforcing Properties of Orally Administered MDMA ('Ecstasy') in Rats

2021 ◽  
Author(s):  
◽  
Lincoln S. Hely
Keyword(s):  
Oral Administration ◽  
Drugs Of Abuse ◽  
Demand Curve ◽  
Subcutaneous Administration ◽  
Route Of Administration ◽  
Schedules Of Reinforcement ◽  
Self Administration ◽  
Onset Of Action ◽  
Reinforcing Efficacy ◽  
Reinforcing Effects

<p>The so-called “party drug” 3,4-Methylenedioxymethamphetamine (MDMA, or ecstasy) may share many of the addictive properties common to other CNS stimulants. In humans MDMA is primarily consumed orally in one more pills per session. However, animal research has mostly focused on examining the effects of MDMA as a function of other routes of administration. Route of administration can have profound effects on the subjective and reinforcing properties of drugs of abuse. This thesis assessed the locomotor-activating and reinforcing properties of MDMA when delivered orally. MDMA-induced hyperlocomotion was used to examine magnitude of response and onset of action as a function of ip, sc and oral administration. Significant route-dependant effects were found with ip producing higher locomotor activity than sc and oral respectively. Onset of action was slower for subcutaneous administration compared with both ip and oral administration. The reinforcing properties of MDMA were examined by use of the self-administration procedure. Oral MDMA self-administration was firstly examined using simple schedules of reinforcement as a function of two different vehicle substrates, water (under water deprivation) and saccharin. Oral MDMA maintained responding and reliable dose-response curves were obtained under both water and saccharin vehicle conditions. However, both saccharin and water vehicle conditions also acted as strong reinforcers in these studies. Further studies utilising a behavioural economic approach were conducted in order to delineate the reinforcing effects of MDMA from that of its parent vehicle. In addition, demand-curve analysis using both the Linear-Elasticity model (Hursh et al., 1988, 1989) and the Exponential Model of Demand (Hursh & Silberberg, 2008) were compared in order to evaluate each model and assess the relative reinforcing efficacy of oral MDMA. Demand curves for the oral self-administration of MDMA revealed that responding for MDMA was more elastic (lower Pmax) than responding for saccharin-alone indicating that saccharin functioned as stronger reinforcer than did MDMA+saccharin. The results of these studies provide evidence for the positive-reinforcing effects of MDMA when it is delivered via the oral route of administration, however, the relative reinforcing efficacy of orally delivered MDMA appears to be low.</p>

scholarly journals Assessment of the Reinforcing Properties of Orally Administered MDMA ('Ecstasy') in Rats

2021 ◽  
Author(s):  
◽  
Lincoln S. Hely
Keyword(s):  
Oral Administration ◽  
Drugs Of Abuse ◽  
Demand Curve ◽  
Subcutaneous Administration ◽  
Route Of Administration ◽  
Schedules Of Reinforcement ◽  
Self Administration ◽  
Onset Of Action ◽  
Reinforcing Efficacy ◽  
Reinforcing Effects

<p>The so-called “party drug” 3,4-Methylenedioxymethamphetamine (MDMA, or ecstasy) may share many of the addictive properties common to other CNS stimulants. In humans MDMA is primarily consumed orally in one more pills per session. However, animal research has mostly focused on examining the effects of MDMA as a function of other routes of administration. Route of administration can have profound effects on the subjective and reinforcing properties of drugs of abuse. This thesis assessed the locomotor-activating and reinforcing properties of MDMA when delivered orally. MDMA-induced hyperlocomotion was used to examine magnitude of response and onset of action as a function of ip, sc and oral administration. Significant route-dependant effects were found with ip producing higher locomotor activity than sc and oral respectively. Onset of action was slower for subcutaneous administration compared with both ip and oral administration. The reinforcing properties of MDMA were examined by use of the self-administration procedure. Oral MDMA self-administration was firstly examined using simple schedules of reinforcement as a function of two different vehicle substrates, water (under water deprivation) and saccharin. Oral MDMA maintained responding and reliable dose-response curves were obtained under both water and saccharin vehicle conditions. However, both saccharin and water vehicle conditions also acted as strong reinforcers in these studies. Further studies utilising a behavioural economic approach were conducted in order to delineate the reinforcing effects of MDMA from that of its parent vehicle. In addition, demand-curve analysis using both the Linear-Elasticity model (Hursh et al., 1988, 1989) and the Exponential Model of Demand (Hursh & Silberberg, 2008) were compared in order to evaluate each model and assess the relative reinforcing efficacy of oral MDMA. Demand curves for the oral self-administration of MDMA revealed that responding for MDMA was more elastic (lower Pmax) than responding for saccharin-alone indicating that saccharin functioned as stronger reinforcer than did MDMA+saccharin. The results of these studies provide evidence for the positive-reinforcing effects of MDMA when it is delivered via the oral route of administration, however, the relative reinforcing efficacy of orally delivered MDMA appears to be low.</p>

The Effect of the Route of Administration of Single Doses of p,Ṕ-DDT on Residues in Adipose and Liver Tissues

1968 ◽  
Vol 51 (5) ◽  
pp. 1050-1057
Author(s):  
K A Mccully ◽  
W P Mckinley ◽  
W E J Phillips
Keyword(s):  
Body Weight ◽  
Oral Administration ◽  
Guinea Pigs ◽  
Intraperitoneal Injection ◽  
Route Of Administration ◽  
The Other ◽  
Intramuscular Administration ◽  
Liver Tissues

Abstract p,Ṕ-DDT was administered orally, intraperitoneally, and intramuscularly (10 mg/kg body weight) to rats, sheep, chickens, rabbits, and guinea pigs. Animals were killed 5 days after dosing and fat and liver samples removed. All animals except chickens stored a greater concentration of total residues in the fat and livers following intraperitoneal injection than by oral or intramuscular administration. Residues in the fat demonstrated that oral administration of p,Ṕ-DDT resulted in greater conversion of p,Ṕ-DDT to p,Ṕ-DDD than administration by the other routes. Conversion appeared to be greatest in sheep (ruminant) and rabbits (functional cecum). Livers of all treated animals contained p,Ṕ-DDD residues, regardless of the route of administration

scholarly journals Cannabis use frequency, route of administration, and co-use with alcohol among older adults in Washington state

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Meenakshi S. Subbaraman ◽  
William C. Kerr
Keyword(s):  
Older Adults ◽  
General Population ◽  
Oral Administration ◽  
Age Groups ◽  
Washington State ◽  
Route Of Administration ◽  
Cannabis Use ◽  
Multinomial Regression ◽  
Sampling Weights ◽  
Routes Of Administration

Abstract Background The US national surveys and data from legal adult use cannabis states show increases in the prevalence of cannabis use among older adults, though little is known about their manner of cannabis consumption. Here, we examine cannabis use frequency, routes of cannabis administration, and co-use with alcohol, focusing on adults aged 50–64 and ≥65. Methods Data come from a general population survey conducted January 2014–October 2016 (N=5492) in Washington state. We first estimate prevalence and trends in cannabis frequency, routes of administration, and co-use with alcohol in gender by age groups (18–29, 30–49, 50–64, ≥ 65). To test associations between cannabis frequency, route of administration, and co-use with alcohol, we then use sample-weighted multinomial regression adjusted for gender, race/ethnicity, marital status, education, employment, and survey year. Sampling weights are used so results better represent the Washington state population. Regressions focus on the 50–64 and ≥65 age groups. Results Among men and women 50–64, the prevalence of no cannabis use in the past 12 months decreased significantly (84.2% in 2014 to 75.1% in 2016 for women, 76.8% in 2014 to 62.4% in 2016 for men). Among those who report past-year cannabis use, oral administration and vaping and other routes of administration increased by 70% and 94%, respectively each year. Almost one-third of women aged 50–64 and one-fifth of women aged ≥65 who use cannabis reported daily/near daily use, and more than one-third of men who use cannabis in all age groups reported daily/near daily use, including 41.9% of those ≥65. Among men, the prevalence of edibles, drinks, and other oral forms of cannabis administration went up significantly with age (6.6% among 18–29, 21.5% among ≥65). Vaping and other administration are more strongly related to regular and daily/near daily use than infrequent use among those ≥65. The pattern of associations between cannabis frequency and co-use with alcohol differed for women vs. men. Conclusions In a general population representative sample of adults living in a state with legal adult use cannabis, the prevalence of cannabis use increased among those aged 50–64 between 2014 and 2016, the prevalence of daily use is substantial, and oral administration and vaping are increasing.

scholarly journals Oral administration of cyanocobalamin for functional vitamin В12 deficiency: efficacy and safety

2021 ◽  
Vol 13 (4) ◽  
pp. 109-115
Author(s):  
E. V. Shikh ◽  
Zh. M. Sizova ◽  
M. O. Astaeva
Keyword(s):  
Oral Administration ◽  
Methylmalonic Acid ◽  
Intrinsic Factor ◽  
Clinical Manifestations ◽  
Serum Vitamin ◽  
Oral Route ◽  
Route Of Administration ◽  
Initial Stage ◽  
Number Of Patients ◽  
Daily Dose

The prevalence of vitamin В12 deficiency is about 3—16% in the general population, while in older people, it ranges from 10 to 20%. An increase in the proportion of people on reduced-calorie diets, the widespread use of drugs that can result in vitamin В12 deficiency, an increase in life expectancy, on the one hand, a variety of clinical manifestations and the lack of precise algorithms for laboratory diagnostics, on the other hand, suggest that the number of patients with vitamin В12 deficiency is significantly higher. Vitamin В12 can be absorbed by passive diffusion, regardless of intrinsic factor and other underlying causes of the deficiency. The presence of an additional route of absorption brings in new expectations for the oral administration of cyanocobalamin in therapeutic doses. Comparative clinical trials of the use of cyanocobalamin have shown that the oral route of administration is as effective as the parenteral. Considering the need for long-term, and in some cases — life-long, use of the drug, there is a need to develop dosage regimens for oral administration comparable in effectiveness to parenteral administration. The use of functional vitamin В12 deficiency biomarkers, such as vitamin В12 levels, cholotranscobalamin, methylmalonic acid, homocysteine, made it possible to establish that a daily dose of 1000 mkg is the most effective, which at the initial stage is as efficient as intramuscular administration. In some circumstances, maintenance therapy (intramuscularly at a dose of 1 mg/month) was more effective; thus, a differentiated approach scheme to determining the maintenance oral dose was proposed, depending on the result obtained at the initial stage of therapy. Comparative studies covering the entire spectrum from the recommended dietary allowance to the dose commonly used for cobalamin injections have shown that an oral daily dose of 1000 mcg of cyanocobalamin normalizes serum vitamin В12 levels and causes an 80—90% decrease in plasma methylmalonic acid concentration from the assumed maximum value. The oral route of administration provides a higher patient treatment adherence.

Letter to the Editor

PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 695-696
Author(s):  
Richard J. Scarfone
Keyword(s):  
Oral Administration ◽  
Respiratory Distress ◽  
Acute Asthma ◽  
Route Of Administration ◽  
Onset Of Action ◽  
Delayed Onset ◽  
Hospitalization Rates ◽  
Letter To The Editor

We appreciate the comments of Drs Perry and Allison. As they pointed out, the oral administration of prednisone, unlike corticosteroids given intramuscularly or intravenously, is not likely to exacerbate the respiratory distress and hypoxemia of an acutely wheezing child. We would like to emphasize that corticosteroids, regardless of the route of administration, have a delayed onset of action in acute asthma. In our study, had decisions regarding hospitalization been made after 2 hours of care, the hospitalization rates of the prednisone and placebo groups would have been about the same.

Trimethoprim-Sulfamethoxazole Pharmacokinetics during Continuous Ambulatory Peritoneal Dialysis (CAPD)

1989 ◽  
Vol 9 (1) ◽  
pp. 51-55 ◽  
Author(s):  
S.E. Walker ◽  
T.W. Paton ◽  
D.N. Churchill ◽  
B. Ojo ◽  
M.A. Manuel ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Oral Administration ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Half Life ◽  
Total Body Clearance ◽  
Route Of Administration ◽  
Adult Patients ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

Ten adult patients on continuous ambulatory peritoneal dialysis (CAPO) received one dose of trimethoprim320 mg (TMP) and sulfamethoxazole 1600 mg (SMX) orally (p.o.), intravenously (i.v.), and intraperitoneally (i.p.) on three separate occasions to characterize the pharmacokinetics of both drugs. Concentrations of both TMP and SMX were measured in serum and dialysate by HPLC to 48 h. Half-life, total body clearance (TBC), and peritoneal clearance (PCI) were determined. The mean half-life of TMP was 28 h, while for SMX it was 12.5 h. Relative to the i.v. dose, the bioavailability following oral administration for TMP was 98% and 87% for SMX. Intraperitoneal bioavailability was 73% for TMP and 65% for SMX after a 4-h dwell. After 24 h, regardless of the route of administration, less than 3% of TMP and less than 6% of SMX appeared in dialysate. We conclude that peritoneal losses contribute insignificantly to TMPISMX elimination during CAPO.

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