- Routes of administration
- First pass metabolism, bioavailablilty, drug distribution,
- Drug interactions with proteins, Drug metabolism, elimination, Half-life
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
A power point presentation on general aspects of Pharmacokinetics suitable for undergraduate medical students beginning to study Pharmacology. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
A power point presentation on general aspects of Pharmacokinetics suitable for undergraduate medical students beginning to study Pharmacology. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
Pharmacodynamics, mechanism of drug actionAsma Aslam
complete information on receptors and their mechanism of actions... briefly discussed about pharmacodynamics and up regulation and desensitization of receptors,
Factors affecting each of the proceses- Absorption, Distribution, Metabolism and Elimination of Drugs and associated Pharmacokinetic Parameters- Bioavailability, Volume of Distribution, Half life of drug, Rate of Clearance
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
For More Medicine Free PPT - http://playnever.blogspot.com/
For Health benefits and medicine videos Subscribe youtube channel - https://www.youtube.com/playlist?list=PLKg-H-sMh9G01zEg4YpndngXODW2bq92w
Pharmacodynamics, mechanism of drug actionAsma Aslam
complete information on receptors and their mechanism of actions... briefly discussed about pharmacodynamics and up regulation and desensitization of receptors,
Factors affecting each of the proceses- Absorption, Distribution, Metabolism and Elimination of Drugs and associated Pharmacokinetic Parameters- Bioavailability, Volume of Distribution, Half life of drug, Rate of Clearance
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
For More Medicine Free PPT - http://playnever.blogspot.com/
For Health benefits and medicine videos Subscribe youtube channel - https://www.youtube.com/playlist?list=PLKg-H-sMh9G01zEg4YpndngXODW2bq92w
Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
Clinical pharmacokinetic studies are performed to examine the absorption, distribution, metabolism, and excretion of a drug under investigation in healthy volunteers and/or patients
MRCPsych I - Suicide and Self Harm (April 2007)Alex J Mitchell
This is an academic educational presentation given for those studying for MRCPsych (Royal College of Psychiatrists) Part I. It is from 2007, Leicester Partnership Trust. Apologies if this is difficult to follow when read in isolation.
General pharmacology Diploma in pharmacy second year YogeshShelake
The General pharmacology ,Toxicology & Pharmacotherapeutics
To Undastanding the general pharmacology & Definitions of PHARMACODYNAMECIS ,PHARMACOKINITICS (Absorbation,Distribution,Metabolism,Excreation )Pharmacology ,Toxicology ,Pharmacotherapeutic ,
Advantages of Routs of Administration & Their Disadvantages
Factors affecting of absorpation ,excreation of drug,factor modifing deug action
Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug's effect on the body more closely.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
2. Objectives - understand
1. Pharmacokinetics and pharmacodynamics
2. Different routes of administration of
medications (advantages and disadvantages)
3. Terms: ‘First pass metabolism’, absorption,
bioavailability, drug distribution .
4. Drug interaction with proteins, drug
metabolism, elimination, half-life
3. What is pharmacology?
Includes:
1.Origins, chemical structure, preparation,
administration, actions, metabolism,
excretion
2.Therapeutics: application of action of drugs
and other measures in the treatment of
disease
4. Pharmacology
• Pharmacology is the study of the action and use
of drugs
• Medical pharmacology is the science of
chemicals (drugs) that interact with the human
body
• Drugs are chemical substances which, by
interacting with biological systems, are able to
change them in some way, or:
• A substance, applied to a living system, with the
intent of bringing about a change
5. Pharmacokinetics
• Refers to the processes concerned with the
distribution of drugs in the body and their:
– Absorption
– Excretion
– Metabolism
• Therefore it is it is concerned with the way in
which the concentration of a drug varies as
per the site of its action and how this is
affected by the of administration
6. Drug at site of
Pharmacokinetics administration
Absorption
Drug in blood
Drug in tissue
Metabolism
Metabolites in tissue
Elimination
Drugs and/or metabolites in
Urine/faeces/bile
7. Absorption
Pharmacokinetics
Blood Stream
Distribution
Tissue Bound
Metabolism Protein bound
Metabolites Elimination
9. Oral
• By mouth
– Common route of administration
• Complicated pathway
• Some of drug is absorbed:
– Stomach
– Duodenum
– Small intestine
• Via the small intestine, it goes via the hepatic
portal vein to the liver before the systemic
circulation
12. First pass metabolism
• All drugs absorbed in the gut go via the liver
to reach the systemic circulation
– In the liver
• Some of the drug is metabolised
• Therefore not all reaches systemic circulation
• E.g. 90% of nitroglycerine is cleared in a single pass
through the liver
14. Sublingual route – under tongue
• Delivers the drug direct to the bloodstream
– Not via the liver and liver metabolism
• E.g. Glyceryl trinitrate
15. Rectal
• 50% of blood bypasses the portal circulation
and liver metabolism
• Avoids stomach and acids/enzymes in GIT
• Useful if the drug causes vomiting when taken
orally.
• E.g. Diazepam (antiepileptic drug)
16. Intravenous injection
Advantages Disadvantages
• For days not absorbed • Drugs cannot be recalled
orally once injected
• Avoids GIT; 1st pass • Site of injection can be
metabolism of liver infected with bacteria
• Rapid effect • Adverse reaction because of
• Maximal degree of control a too rapid delivery of high
over circulating levels of concentration of drug to
drugs blood and tissues (infusion
rate must be controlled)
17. Intramuscular injection
• Must be aqueous preparation or specialised
‘depot’ preparation (suspension in ethylene
glycol or peanut oil)
– Aqueous suspension
• Absorbed quickly
– Depot suspension
• Absorbed slowly
• E.g. Haloperidol – anti-schitzophrenic drug
21. Other routes of administration
• Inhalation
• Intranasal
• Topical (ointment/creams)
• Transdermal (patches)
• Intrathecal (into spinal canal)
22. Absorption of drugs
• Drugs absorbed from gut by
– Diffusion (across GIT wall into blood)
– Active transport (via carrier proteins in plasma membrane;
active process)
• pH (acid/alkaline environment) influences drug absorption
• Physical factors influencing absorption
– Blood flow through the absorption site
– Total surface area available for drug absorption
– Contact time at absorption site (e.g. Poor absorption with
diarrhoea)
– Presence of food in stomach
• Dilutes drug
• Slows stomach emptying
23. Bioavailability
• Fraction of the administered drug that
reaches the systemic circulation
• E.g. If 100mg of drug is administered and
70mg of drug is absorbed unchanged:
• Bioavailability is 70%
26. Bioavailability – affecting factors
• 1st pass metabolism
• Solubility of drugs
– If hydrophilic: poorly absorbed because can’t cross
lipid bilayer of plasma membrane
– Highly hydrophobic: poorly absorbed because
insoluble in aqueous body fluids
– Drugs need to be hydrophobic, but have some
solubility in aqueous solution
• Chemical instability
– Penicillin: unstable because of pH in stomach
– Insulin: may be destroyed by GIT enzymes – injected
• Nature of drug formulation
27. Drug distribution
• Drug distribution refers to the movement of
the drug to/from the blood and various
tissues of the body (e.g. Fat, muscle, brain)
and the relative proportion of the drug in the
tissues
• This depends on blood flow;
– Brain, liver, kidney>skeletal muscle>adipose tissue
– Capillary structure
– Drug structure(hydrophilic/phobic)
– Binding of drugs to blood plasma protein
30. Drugs and blood plasma proteins
• Main influence of plasma proteins on drugs is in their distribution
• The most important plasma proteins are
– Albumin, acid-glycoprotein, β-globulin
• Once a drug is absorbed into the circulation, it can become protein-bound
• This plasma protein binding can be rapidly reversible and is non-specific
– Many drugs can bind to one protein
• But the plasma proteins are not the target tissue and drugs that are
bound to them cannot bring about a physiological effect, however:
• Drug/protein binding can form a reservoir of the drug
– Only free (unbound) drug is available to the tissues to exert a
therapeutic effect.
31. Effect of protein binding on drug action?
• If protein binding does occur, the behaviour of
the drug can be influenced:
1. Extensive protein binding reduced available free
(unbound) drug; therefore more drug has to be
administered to get therapeutic effect
2. Elimination of a highly bound drug may be
delayed
• If the free drug is low, the total drug
elimination/excretion is delayed
– E.g. This is the reason for the prolonged effect of digoxin
32. Effect of protein binding on drug action?
• 3 – Low plasma concentration may result
in old age
• Can get reduced plasma protein concentration
with liver disease (made there), or chronic
renal failure causing xs protein loss in urine
– Increased free drug; decreased bound drug
– Increased free drug; reduced drug dose needed
33. Effect of protein binding on drug action?
• 4 – different drugs can compete for the
binding sites on plasma proteins, leading to
interactions
– E.g. Warfarin (anticoagulant) is highly bound and
even a small change in binding will greatly effect
the amount of free drug
– Therefore if there is administration with (e.g.)
aspirin, the aspirin displaces the warfarin causing
an increase in free anticoagulant
35. Drug metabolism 1
• Metabolism is the enzymic conversion of one
compound into another
– Mostly occurs in the liver, but also in gut wall, lung
and blood plasma
• Generally, the metabolism of a drug converts in
into a more water soluble compound with more
polarity
– This is important as it can only be excreted in urine an
bile
– Few drugs are excreted without being metabolised
• Generally, as drug is metabolised, its therapeutic
effect decreases
36. Drug metabolism –2
• Liver hepatocytes have all the necessary
enzymes for the metabolism of drugs
– Main enzyme involved in drug metabolism belong
to the cytochrome P450 group.
• These are a large family of related compounds housed
in the smooth endoplasmic reticulum of the cell
– Metabolism is often divided into phase 1 and
phase 2
• Some drugs just need to undergo either phase 1 or 2
• More often need phase 1, then phase 2
37. Drug metabolism 3
• Phase 1 metabolism can be reduction or
hydrolysis of a drug, but is usually oxidation
• Oxidation is catalysed by cytochrome P450
– One electron removed
• Drug is now oxidised; but even after phase 1
metabolism it can still be chemically active
39. Drug metabolism - 4
• Phase 2 metabolism involves conjugation
– an ionised group is attached to the drug
• Groups included glutathione, methyl or acetyl groups
– Usually occurs in hepatocyte cytoplasm
• The attachment of the ionised group makes the
drug more water soluble
– Facilitates excretion
– Decreases pharmacological activity
• E.g. Aspirin
– Phase 1 undergoes hydrolysis to salicylic acid
– Phase 2 is conjugated with either glycine or glucuronic
acid
• Forming a range of metabolites that can be excreted
40. Drug metabolism - 5
• Some drugs are administered in inactive form, or prodrug,
e.g. Enalapril
– It’s metabolite is pharmacologically active
• Enalaprilat – antihypertensive
• Some drug metabolites can be toxic
– E.g. Those produced from paracetamol phase 1 metabolism
– These are detoxed by phase 2 conjugation with glutathione
• In overdose situations, where the dose of paracetamol is
high, not enough glutathione is available to detox the
metabolites
– accumulates causing toxicity – hepatitis
– As a solution, compounds are administered to boost levels of
glutathione so that phase 2 can take place; thus paracetamol is
metabolised fully and reduces the risk of liver damage
41. Drug metabolism - 6
• Affecting factors
– Age: reduced numbers of hepatocytes and
enzymic activity
– Diseases that reduce blood flow to liver (heart
failure/shock) reduce its metabolic activity
– Genetic deficiency – re one enzyme
– Other drugs and diet etc that reduce liver function
• E.g. Grapefruit juice and St john’s Wort
– Inhibit cytochrome P450
• Smoking and brussel sprouts
– Increase P450 activity
42. Elimination and half life - (t½)
• The duration of the drug in the body is called its half-life (t½)
• The t½ is the period of time for the concentration/amount of a drug
in the body to be reduced by half
• Usually the t½ is used in reference to its plasma concentration
• The drug may not be in the plasma; if it leaves:
– may be in another body fluid compartment (intracellular fluid)
– Destroyed in plasma
• The removal of a drug from the plasma
– Clearance
• The distribution of a drug in various body tissues
– Volume of distribution
• The clearance and volume of distribution are important in
determining the t½
49. Elimination
• Elimination is the process by which the drug (and its
metabolites) is eliminated fro the body without further
chemical change
• Most drugs are metabolised prior to excretion
– Some drugs (e.g. Aminoglycoside antibiotics) are polar
compounds (hydrophilic) and are excreted by the kidneys
without being metabolised first
• The kidneys are the major excretory organs and excrete
water soluble drugs
• The biliary system contributes to excretion if the drug is
secreted in bile and then is not reabsorbed from the GIT
• There are small contributions from:
– Intestines, saliva, sweat, breast milk and lungs
• Excretion via breast milk may not be of importance to the mother, but
may be to the suckling child
50. Renal excretion
• Excretion of the drug via the kidneys uses 3
processes, all of which occur in the nephron
– Glomerular filtration
– Tubular secretion
– Tubular reabsorption
54. Glomerular filtration
• The drug goes to the kidney via the blood
• From the glomerulus it passes into the
glomerular (Bowman’s) capsule as part of the
filtrate
• Large drugs, e.g. Heparin, or those bound to
plasma proteins, cannot be filtered and
therefore cannot be excreted
55. Tubular resorption
• Drugs and their metabolites enter the filtrate
in the nephron, but some may be resorbed
• Resorption occurs as diffusion (not active)
• Occurs because water is resorbed by osmosis
– The majority of water that enters the nephron is
resorbed back in to the blood (to maintain body
fluid volume) and the drug follows it by diffusion
56. Urine pH - 1
• Urine pH has a great influence on how fast a
drug is excreted
• This can be manipulated in a clinical situation
to control the excretion of certain drugs from
the body
57. Urine pH- 2
• Most drugs are either weak acids or bases (alkaline)
– In alkaline urine, acidic drugs are more readily ionised
– In acidic urine, alkaline drugs are more readily ionised
• Ionised substances are more polar and so are dissolved
and excreted more readily
• This is important in situations like blood poisoning;
drug must be excreted rapidly from the body
– One strategy is to alter urine pH to increase excretion
– E.g. Aspirin poisoning: making the urine more alkaline with
sodium bicarbonate increases the ionisation of salicylic
acid (aspirin metabolite) and increases it excretion from
the body
58. Tubular secretion - 1
• Most drugs don’t enter the nephron via the
glomerular filtrate, but by tubular secretion
– Active process: drugs are carried against their
diffusion gradient, from the capillary network into
the tubular filtrate
• Tubular secretion involves 2 carrier systems:
– Basic (alkaline) carriers: transport basic drugs
(amiloride, dopamine, histamine)
– Acidic carriers: transport acidic drugs (frusemide,
penicillin, indomethacin)
59. Tubular secretion - 2
• Tubular secretion can have a big impact on
the speed that a drug is eliminated from the
body; e.g. Penicillin is readily secreted into the
tubular filtrate and rapidly excreted in urine
• If the therapeutic effect needs to be
prolonged/maintained, agents can be
administered that block tubular secretion,
thus slowing the excretion of the drug
61. Biliary secretion
• Drugs and metabolites that are secreted in
bile are transported across the biliary
epithelium against their concentration
gradient (active)
– Affecting factors
• Blood concentration: if high, bile content will be high
• If drugs with similar physiochemical properties are
present together, they can compete for the transport
mechanisms
62. Biliary secretion
• Drugs that are more likely to be excreted into
bile have a molecular weight of >300g/mol
– Smaller, only in negligible amounts
– Both bipolar and lipophilic are excreted
– Conjugation (especially with glucuronic acid) leads
to biliary excretion