Effects of Food on Bioavailability of Analgesics; Resulting Dosage and Administration Recommendations

Pain Medicine ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 2877-2892
Author(s):  
Suresh Babu Naraharisetti ◽  
Salma Srour ◽  
Yun Xu ◽  
David J Lee ◽  
Sharon H Hertz ◽  
...  

Abstract Objectives To evaluate currently approved analgesics, that is, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and serotonin and norepinephrine reuptake inhibitors (SNRIs) used as analgesics, for 1) differences in pharmacokinetic parameters under fed vs fasting conditions and 2) factors involved in dosage recommendations in relation to food. Design Systematic review. Results Food effect on the rate, extent of absorption, or shape of concentration–time profile can alter the onset of action, duration of action, or tolerability of a medication. Based on 79 analgesic products reviewed, food effect dosage recommendations depend on whether an analgesic will be dosed on a regular interval around-the-clock vs on an as-needed basis, the shape of concentration–time profile, steady-state concentrations, the type of meals used in the pharmacokinetic study, and drug administration with regard to food in clinical trials. Overall, most opioids do not have food restriction and are taken without regard to food, with the exception of OPANA products and XTAMPZA ER. For many NSAIDs, food does not affect absorption characteristics, with the exception of ZORVOLEX and CELEBREX. Although NSAIDs are commonly to be taken without regard to food, prescribers recommend administering them with food to reduce their propensity for gastrointestinal adverse events. A larger percentage of anticonvulsants and SNRIs used as analgesics are taken with food to improve their tolerability. Of all analgesic products, seven NSAIDs and six opioids lack food effect information, maybe due to their approval before Food and Drug Administration food effect guidance. Conclusions Overall, because food effects could alter the onset and/or duration of pain relief, analgesic medication should be used as per labeled recommendations for proper pain management.

2021 ◽  
Vol 1 (1) ◽  
pp. 035-045
Author(s):  
Manish S. Junagade ◽  
Anju Goyal

A clinically useful drug may have limitations in practice because of undesirable side effects, poor solubility, and poor bioavailability, short duration of action, first-pass effect, poor absorption & adverse effects. There are increased efforts in research to increase the therapeutic efficacy of drugs by eliminating or minimizing the undesirable properties of drug molecules. Some of the problems can be solved using a formulation development approach but in some cases, chemical modification in the molecule is necessary to correct the pharmacokinetic parameters. One of the approaches to convert the existing molecule to a more efficient molecule is prodrug design. Mutual Prodrug is the molecule in which an active drug molecule is attached to a carrier molecule having pharmacological activity. So a mutual prodrug consists of two pharmacologically active molecules connected by a bio labile linkage. Both molecules in this act as a pro moiety of each other. The design of mutual prodrug is very fruitful in the area of research & has given successful results in increasing the clinical & therapeutic effectiveness of the drugs. The present article takes a review of various applications of mutual prodrugs & development in this field in the last few decades.


1998 ◽  
Vol 42 (3) ◽  
pp. 631-639 ◽  
Author(s):  
Richard Hafner ◽  
James Bethel ◽  
Maureen Power ◽  
Bernard Landry ◽  
Mary Banach ◽  
...  

ABSTRACT This study evaluated the tolerance and potential pharmacokinetic interactions between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in clinically stable human immunodeficiency virus-infected volunteers with CD4 counts of <200 cells/mm3. Thirty-four subjects were randomized equally to either regimen A or regimen B. On days 1 to 14, subjects assigned to regimen A received clarithromycin and subjects assigned to regimen B received rifabutin, and then both groups received both drugs on days 15 to 42. Of the 14 regimen A and the 15 regimen B subjects who started combination therapy, 1 subject in each group prematurely discontinued therapy due to toxicity, but 19 of 29 subjects reported nausea, vomiting, and/or diarrhea. Pharmacokinetic analysis included data for 11 regimen A and 14 regimen B subjects. Steady-state pharmacokinetic parameters for single-agent therapy (day 14) and combination therapy (day 42) were compared. Regimen A resulted in a mean decrease of 44% (P = 0.003) in the clarithromycin area under the plasma concentration-time curve (AUC), while there was a mean increase of 57% (P = 0.004) in the AUC of the clarithromycin metabolite 14-OH-clarithromycin. Regimen B resulted in a mean increase of 99% (P = 0.001) in the rifabutin AUC and a mean increase of 375% (P < 0.001) in the AUC of the rifabutin metabolite 25-O-desacetyl-rifabutin. The usefulness of this combination for prophylaxis of Mycobacterium avium infections is limited by frequent gastrointestinal adverse events. Coadministration of clarithromycin and rifabutin results in significant bidirectional pharmacokinetic interactions. The resulting increase in rifabutin levels may explain the increased frequency of uveitis observed with concomitant use of these drugs.


2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Shihua Xing ◽  
Mengyue Wang ◽  
Ying Peng ◽  
Xiaobo Li

Baicalin and wogonoside are two of the most abundant flavonoid glycosides in the root of Scutellaria baicalensis Georgi, which is a widely used peroral herbal medicine with anticancer, antiviral, antibacterial and anti-inflammatory properties. In the present study, the effects of intestinal microecology on the metabolism and pharmacokinetics of orally administered baicalin and wogonoside were investigated by UPLC-QTOF/MS measurement of the difference in metabolites between normal and antibiotic-pretreated rats. In the antibiotic-pretreated rats, the plasma concentration-time profile and pharmacokinetic parameters of the two flavonoid glycosides and their relevant aglycone forms were significantly changed compared with those in normal rats. Further, hydrolysis and glucuronidated metabolites were not detected in the cecum contents and urine samples from antibiotic-pretreated rats. These results suggested that intestinal microbiota may play a key role in the pharmacokinetics and metabolism of peroral baicalin and wogonoside. According to our findings, it is recommended that the root of S. baicalensis should not be co-administered with antibiotics in clinical use.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Chunchao Han ◽  
Bo Cui

The purpose of this study is to investigate the bioavailability and glycaemic metabolism of cinnamon oil (CIO) carried by liquid-loadable tablets (CIO-LLTs), the carrier of a CIO self-emulsifying formulation (CIO-LS). The results of tests performed to evaluate the physical properties of the CIO-LLT complied with Chinese Pharmacopeia (2010). The release profile suggested that the CIO-LLT preserved the enhancement of in vitro dissolution of cio. After orally administration, the plasma concentration-time profile and pharmacokinetic parameters suggested that a significant increase (P<0.0001) in theCmax, AUC andFwere observed in the CIO-LLT. The blood glucose and the HbA1c were significantly decreased in alloxan-induced hyperglycemic rats (P<0.05,P<0.01, resp.), while the level of insulin secretion was markedly elevated in alloxan-induced hyperglycemic rats (P<0.05). The alloxan-damaged pancreaticβ-cells of the rats were partly recovered gradually after the rats were administered with CIO-LLT 45 days later. CIO-LLT could improve the bioavailability and glycaemic metabolism of CIO.


2019 ◽  
Vol 104 (6) ◽  
pp. e3.2-e3
Author(s):  
A Pansari ◽  
K Abduljalil ◽  
T Johnson

BackgroundCaffeine has been extensively used in the treatment of apnoea in premature infants,1 its disposition varies with postnatal age2 and can differ markedly between premature and term neonates.MethodsThe Preterm population within the Simcyp Simulator V18R1 population library was used to replicate clinical studies to predict caffeine exposure after single3 and multiple4 intravenous administration to preterm neonates of gestational weeks 28.5 and 29 (28–33) respectively, ranging in postnatal age of 3–30 days and 0–3 days respectively. Predictive performance of the Physiologically Based Pharmacokinetic Model (PBPK) was evaluated by comparing the simulated to the clinical results. A population simulation was performed for the single dose study as only pharmacokinetic parameters were available. However, for multiple doses study, where individual plasma concentration-time profile data were available, simulations were performed for each individual.ResultsPBPK model predictions for caffeine in preterm neonates were in good agreement with the clinical observations. In the case of single dose administration, the ratios of predicted vs observed mean Volume of distribution (Vss), peak plasma concentration (Cmax), Clearance (CL) and Half-life (t1/2) were 1, 1.2, 1 and 1.1, respectively. Individual predicted concentration-time profiles following multiple dose administration were in close agreement with the observed data for all 16 subjects, overall 95% of individual observed data points were within the 5th and 95th percentile of predicted plasma concentration-time profile.ConclusionsThe predictive performance of preterm PBPK models for caffeine was found to be appropriate. A similar PBPK approach can be utilized in the clinics for the accurate prediction of pharmacokinetic parameters and plasma concentrations and for dosage adjustment to attain specific plasma concentrations of drugs in premature population.ReferencesGiacoia, et al. Effects of formula feeding on oral absorption of caffeine in premature infants. Dev Pharmacol Ther 1989; 12:205–210.Johnson, et al. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet 2006; 45(9):931–56.Aranda, et al. Population Pharmacokinetic profile of caffeine in the premature newborn infant with apnea; The Journal of Pediatrics 1979; 94(4.):663–668.Lee, et al. Caffeine in apnoeic asian neonates: a sparse data analysis. Br J Clin Pharmacol 2002; 54:31–37.Disclosure(s)Nothing to disclose


2009 ◽  
Vol 5 (3) ◽  
pp. 810-818 ◽  
Author(s):  
Serife Evrim Kepekci Tekkeli ◽  
Mustafa Volkan Kızıltaş ◽  
Demet Dinçel

A sensitive and selective HPLC method with fluorometric detection was developed for the determination of saxagliptin (SGX) in human plasma and applied to a pharmacokinetic study. SGX was precolumn derivatized with fluorescamine, and the fluorescent derivative was separated on an RP C18 column using a mobile phase composed of acetonitrile-10 mM orthophosphoric acid by isocratic elution with flow rate of 1.3 ml/min. The method was based on the measurement of the derivative using fluorescence detection at 378 nm, with excitation at 463 nm. The calibration curve was linear over the range of 3.0–100.0 ng/ml. LOD and LOQ were found to be 0.15 and 0.5 ng/ml, respectively. Intraday and interday RSD values were less than 2.84%. The plasma concentration–time profile and pharmacokinetic parameters such as AUC0–t, AUC0–∞, Cmax, tmax, t1/2, were calculated according to the assays.


Cornea ◽  
1993 ◽  
Vol 12 (3) ◽  
pp. 228-232 ◽  
Author(s):  
James C. Liu ◽  
Thomas L. Steinemann ◽  
Marguerite B. McDonald ◽  
Hilary W. Thompson ◽  
Roger W. Beuerman

2010 ◽  
Vol 54 (8) ◽  
pp. 3225-3232 ◽  
Author(s):  
Claudia Michael ◽  
Uta Bierbach ◽  
Katrin Frenzel ◽  
Thoralf Lange ◽  
Nadezda Basara ◽  
...  

ABSTRACT The aim of this study was to investigate the pharmacokinetics and safety of voriconazole after intravenous (i.v.) administration in immunocompromised children (2 to 11 years old) and adults (20 to 60 years old) who required treatment for the prevention or therapy of systemic fungal infections. Nine pediatric patients were treated with a dose of 7 mg/kg i.v. every 12 h for a period of 10 days. Three children and 12 adults received two loading doses of 6 mg/kg i.v. every 12 h, followed by a maintenance dose of 5 mg/kg (children) or 4 mg/kg (adults) twice a day during the entire study period. Trough voriconazole levels in blood over 10 days of therapy and regular voriconazole levels in blood for up to 12 h postdose on day 3 were examined. Wide intra- and interindividual variations in plasma voriconazole levels were noted in each dose group and were most pronounced in the children receiving the 7-mg/kg dose. Five (56%) of them frequently had trough voriconazole levels in plasma below 1 μg/ml or above 6 μg/ml. The recommended dose of 7 mg/kg i.v. in children provides exposure (area under the concentration-time curve) comparable to that observed in adults receiving 4 mg/kg i.v. The children had significantly higher C max values; other pharmacokinetic parameters were not significantly different from those of adults. Voriconazole exhibits nonlinear pharmacokinetics in the majority of children. Voriconazole therapy was safe and well tolerated in pediatric and adult patients. The European Medicines Agency-approved i.v. dose of 7 mg/kg can be recommended for children aged 2 to <12 years.


2009 ◽  
Vol 43 (4) ◽  
pp. 726-731 ◽  
Author(s):  
He-Ping Lei ◽  
Guo Wang ◽  
Lian-Sheng Wang ◽  
Dong-sheng Ou-yang ◽  
Hao Chen ◽  
...  

Background: Ginkgo biloba is one of the most popular herbal supplements in the world. The supplement has been shown to induce the enzymatic activity of CYP2C19, the main cytochrome P450 isozyme involved in voriconazole metabolism. Because this enzyme exhibits genetic polymorphism, the inductive effect was expected to be modulated by the CYP2C19 metabolizer status. Objective: To examine the possible effects of Ginkgo biloba as an inducer of CYP2C19 on single-dose pharmacokinetics of voriconazole in Chinese volunteers genotyped as either CVP2C19 extensive or poor metabolizers. Methods: Fourteen healthy, nonsmoking volunteers–7 CYP2C19 extensive metabolizers (2C19*1/2C19*1) and 7 poor metabolizers (2C19*2/2C19*2)–were selected to participate in this study. Pharmacokinetics of oral voriconazole 200 mg after administration of Ginkgo biloba 120 mg twice daily for 12 days were determined for up to 24 hours by liquid chromatography–electrospray tandem mass spectrometry in a 2-phase randomized crossover study with 4-week washout between phases. Results: For extensive metabolizers, the median value for voriconazole area under the plasma concentration–time curve from zero to infinity (AUC0-00) was 5.17 μg•h/mL after administration of voriconazole alone and 4.28 μg•/mL after voriconazole with Ginkgo biloba (p > 0.05). The other pharmacokinetic parameters of voriconazole such as AUC0-24, time to reach maximum concentration, half-life, and apparent clearance also did not change significantly for extensive metabolizers in the presence of Ginkgo biloba. Pharmacokinetic parameters followed a similar pattern for poor metabolizers. Conclusions: The results suggest that 12 days of treatment with Ginkgo biloba did not significantly alter the single-dose pharmacokinetics of voriconazole in either CYP2C19 extensive or poor metabolizers. Therefore, the pharmacokinetic interactions between voriconazole and Ginkgo biloba may have limited clinical significance.


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