Medication of elephants follows the same principles as medication of other species. It is important to remember general principles, including the pharmacodynamics and pharmacokinetics of the drug concerned, and the general advantages and disadvantages of different medication routes. However, there are some special considerations for elephants, related to their size and anatomy.

• While in theory drug dosages should be chosen based on pharmacokinetic studies, in practice, doses for elephants generally have been chosen in an arbitrary manner, based on clinical experience, since there are only a few published pharmacokinetic studies on drugs in elephants. (J375.1.w1, P64.1.w2, P68.1.w1)

• --

• Elephants are monogastric, with microbial fermentation taking place in the large intestine, not in a rumen (B10.49.w12, B212.w9, B387.w4, B451.1.w1); in general it is probably more appropriate to extrapolate from horses for drug dosing than from ruminants.
• It must be remembered that there may be differences in the pharmacokinetics of a given drug in the different elephant species; some preliminary work with NSAIDs has suggested such a difference. (B336.53.w53)
• Some general principles of pharmacokinetics can be used. For example, oral preparations may be divided into four basic groups depending on their solubility and permeability (see: Understanding Pharmacokinetics for Pain Management in Ruminants - Dosage Forms and Drug Properties).
• As with all animals, the elephant's age and physical condition should be considered in determining drug doses, as well as its body weight (known or estimated - see below: Estimating body weight) and potential toxic effects of the drug. (B10.49.w21)

Different methods of scaling of doses to allow for body size include simple scaling by body weight, use of body surface area, and allometric scaling. It should be noted that all scaling methods have their limitations, which have been discussed in Understanding Pharmacokinetics for Pain Management in Ruminants - Dosage Calculations.

Allometric scaling:

• "Allometric (metabolic) scaling involves the concept of the relationships of organic function and systems to body size." (P68.1.w1)

• Various biological parameters such as cardiac output, capillary density, kidney filtration rate and oxygen consumption have a logarithmic linear relationship with body weight and metabolic scaling is based on converting body weight to metabolic size. (P68.1.w1)

• However, dosage determination from studies carried out on elephants to date have shown considerable differences from doses worked out by allometric scaling: (P68.1.w1)

  • Amikacin: pharmacokinetic dose 6-8 mg/kg every 24 hours, versus metabolic scaling dose 2.7 mg/kg every 40 hours; (P68.1.w1)

  • Amoxycillin: pharmacokinetic dose 11 mg/kg every 24 hours, versus metabolic scaling dose 15 mg/kg every 20 hours; (P68.1.w1)

  • Procaine G Penicillin (Penicillin G) pharmacokinetic dose 2500 - 4500 IU/kg every 24/96 hours, versus metabolic scaling dose 12,0000 IU/kg every 40 hours; (P68.1.w1)

  • Trimethoprim-sulphonamide: pharmacokinetic dose 22 mg/kg every 12 hours versus metabolic scaling dose 15 mg/kg every 40 hours. (P68.1.w1)

  • Note: for some drugs the metabolic scaling dose would be too high compared to the dose worked out by pharmacokinetics, and in others, too low. (P68.1.w1)

• Allometric scaling may not be applicable for drugs with pharmacokinetics which are affected by factors such as protein binding of the drug, activity of hepatic enzymes, enterohepatic cycling and urine pH: factors which are not themselves allometrically scaled. (J215.25A.w1)

• In general, scaling across species (or even within a species) by the allometric approach is likely to be appropriate (only) for drugs which: (B270.3.w3, J215.25A.w1)
  • a) have low protein binding; (B270.3.w3, J215.25A.w1) and
  • b) are eliminated primarily by renal mechanisms or by blood flow-limited hepatic (or other) metabolism, rather than by enzyme capacity-limited metabolism. (B270.3.w3, J215.25A.w1)
• There are many exceptions to allometric scaling; while allometric scaling might be useful in some circumstances it could also result in either ineffective dosing or toxic effects. (B13.17.w16, B23.77.w12), 

Dosing by body weight:

• It has been suggested that dose for drugs in elephants should be calculated at the same dose per kilogram as those determined for horses or cattle. (B10.49.w21, B23.77.w12)
• A study comparing the plasma half-life of oxytetracycline in mammal and bird species of different sizes following intravenous administration, found that t_{1/2 β} varied by about 14-fold across the size range and gave an allometric equation: t_{1/2 β = 160} W^0.20 for this drug, across eutherian mammals only, t_{1/2 β = 160} W^0.22 . However, it was also noted that bodyweight only accounted for 36% of total variation in half-life between species. The equation suggested a predicted elimination half-life for elephants of 878 minutes [Editor's note: it should be noted that the studies in horses, with assumed bodyweights of 500 kg, gave t_{1/2 β} varying from 482 - 942 minutes]. (J21.48.w1)

It is clear that there is a need for more pharmacokinetic studies of drugs in elephants. There is also a need to consider possible differences in drug pharmacokinetics between the different elephant species. (P68.1.w1)

• Understanding Pharmacokinetics for Pain Management in Ruminants

This "Elephants: Disease and Treatment" Wildpro volume does not cover roping, nor does it include details of sedation and anaesthesia (these should be included in a later Wildpro volume, "Elephants: Health and Management"). However, for convenience, doses of some sedatives have been provided on the following pages:

• Butorphanol
• Diazepam
• Ketamine
• Morphine
• Medetomidine
• Xylazine

• Intramuscular Injection of Elephants
• Intravenous Injection of Elephants

All the normal advantages and disadvantages of different drug administration routes are applicable to elephants. These have been considered in detail in Routes of Drug Administration in Ruminants. Pharmacokinetic considerations associated with different drug administration routes have been outlined in Understanding Pharmacokinetics for Pain Management in Ruminants - Drug Absorption.

• When considering oral medication, the domestic animal model closest to the elephant in terms of gastro-intestinal anatomy is the horse. (B10.49.w12, B212.w9, B387.w4)
  • Note: the elephant's stomach is very large; the large volume of ingesta present might dilute and bind drugs which are given orally. (J375.1.w1)
• As with other hindgut fermentors, oral administration of antimicrobials may adversely affect the colonic microflora, resulting in severe enteritis. (J375.1.w1)

Additional considerations specific to elephants

• Potential risks to handlers and veterinarians while administering medication;
  • Elephants may be more dangerous when sick or injured and subjected to pain, stress, drug administration and other treatments.
  • The safety of personnel must be considered before an elephant is treated.
• Limitations imposed by management methods such as no contact management;
• The thick skin of elephants, with associated risks of insufficient penetration and subcutaneous deposition when intramuscular injection was intended;
• The tendency of elephants to develop abscesses following intramuscular injections;
• The risk of sloughing when certain drugs are given into the ear veins;
• Practicalities associated with required drug quantities, such as the need for multiple injection sites if large volumes are to be given intramuscularly.
• Anatomical constraints:
  • Intraosseous drug delivery is not practical, since the leg bones are very large and dense with only limited marrow spaces. (J375.1.w1)
  • The intrathoracic and intraperitoneal routes are not useable due to the thickness of the chest and body wall. (J375.1.w1)

(B10.49.w21, B23.77.w12, J196.72.w1, J375.1.w1, P64.1.w2, W580.Aug2005.w1)

Further information on specific drug administration routes in elephants is provided in:

• Intramuscular Injection of Elephants
• Intravenous Injection of Elephants
• Subcutaneous Injection in Elephants
• Rectal Administration in Elephants
• Regional Digital Intravenous Perfusion in Elephants

Note:

• For long-term repeated medication, such as with anti-tubercular drugs, the rectal route has been found to be very useful and to provide appropriate absorption. (J3.120.w3, P503.1.w4, W580.Aug2005.w1)
• If management strategies allow, it may be advantageous to train elephants to accept drug administration techniques before they are actually required.
• Behaviours of a well-trained elephant useful for administration of medication include lowering the head (allowing access to the inner surface of the ear), raising the trunk and opening the mouth, allowing the trunk tip to be handled, lying down (sternal or lateral) and presenting the feet. (J375.1.w1)
• If an elephant restraint device is to be used successfully for medication then the elephant should be trained to enter the restraint device daily. (J375.1.w1)
  • Effective use of such a device requires the elephant to cooperate, entering the device and remaining calm once in the device. (J375.1.w1)
  • Elephants subjected to painful or other unpleasant experiences every time they enter the restraint area may not cooperate to enter on another occasion. (J375.1.w1)

• Routes of Drug Administration in Ruminants
• Intramuscular Injection of Elephants
• Intravenous Injection of Elephants
• Subcutaneous Injection in Elephants
• Rectal Administration in Elephants
• Regional Digital Intravenous Perfusion in Elephants

• Less cooperation from the elephant is required generally for application of topical treatment than for other medication routes. (J375.1.w1)

Baths

• Baths may be used for routine maintenance of good skin condition and for treatment of specific skin problems. (J375.1.w1)
  • To soften and remove excess dead skin, bathing with mineral oil may be used in combination with scrubbing the skin with a wire brush. (J375.1.w1)
  • For superficial bacterial infections, the elephant can be bathed with an iodophore solution or scrub. (J375.1.w1)

Wound dressings 

• Powders, ointments, sprays etc. may be applied locally to wounds. (J375.1.w1, W580.Aug2005.w1)
  • Elephants may rub these off, remove them with their trunk, or pack wounds with dirt.
  • Keeping the area clean may be more important than use of topical medication. (W580.Aug2005.w1)
  • Zinc oxide ointment adheres well and encourages granulation tissue. (W580.Aug2005.w1)
  • For leg wounds, powder products are generally preferred. (W580.Aug2005.w1)
• Bandages placed over topical medication may help keep the medication in the correct place, if the site can be bandaged effectively. (J375.1.w1)
  • Bandages can be used on the lower leg, but are usually removed by the elephant after a short time. (W580.Aug2005.w1)
• It may be necessary for the elephant's handler to remain with the elephant to stop it from removing locally applied medication or bandages. (J375.1.w1)

Foot soaks

• Foot soaks and medications kept in contact with the foot within a boot are used for treatment of superficial infections of the foot (Pododermatitis in Elephants, Sole Abscess in Elephants)
  • Appropriate medications for foot soaks include an antibiotic solution or a disinfectant, such as chlorhexidine, povidone iodine or 5% copper sulphate. Dimethyl sulfoxide (DMSO) may be added to the foot soaking solution. (B22.34.w12, P1.1996.w2)
  • While solutions may have only a superficial effect, rather than penetrating to deeper infected tissues, soaking helps to soften the tissues, so that necrotic areas may be removed. (J375.1.w1)
  • Dimethyl sulfoxide (DMSO) may be added to the foot soaking solution to assist penetration into deeper tissues. (B22.34.w12, J375.1.w1, P1.1996.w2)
  • Inappropriate use of substances which are caustic or toxic may cause complications. (J375.1.w1)
• For treatment of deeper tissues see: Regional Digital Intravenous Perfusion in Elephants
• Topical administration may be used for systemic treatment with some drugs such as avermectins. J375.1.w1
  • Preliminary data indicates that topical administration of 250 µg/kg bodyweight doramectin in two elephants resulted in plasma concentrations greater than 0.2 ng/mL for at least nine days. (J375.1.w1)
  • It may be possible to use topical application of opioid narcotics such as fentanyl; opium paste has been used for centuries, placed into the elephant's mouth. (J375.1.w1)

Ocular treatment

• Most elephants, even if well trained and generally cooperative, reset having the area around the eye manipulated and will close their eye if an attempt is made to place medication on the cornea or conjunctiva. Opening an elephant's eyelids against its will is difficult or impossible. (J375.1.w1, W580.Aug2005.w1)
  • Aqueous drugs may be sprayed onto the eye from a syringe (J375.1.w1) or a small spray bottle. (W580.Aug2005.w1)
    • A spray bottle of medication (e.g. gentamicin in sterile saline) can be given to the elephant's handler, to be sprayed into the eye on an opportunistic basis. (W580.Aug2005.w1)
  • Ointments may be placed into the medial canthus; once the elephant opens its eye, blinking should spread the ointment over the eye. (J375.1.w1)

• --

Taking linear measurements of elephants for weight estimation:

• Body length:
  • Note: "body length" is defined differently in different texts. Mammalogists generally refer to the "head and body length" of an animal, from the nose tip to the base of the tail; those lengths are given in the species pages. This is NOT the same as the various "body length" measurements used for weight estimation.
  • This is taken from the base of the forehead to the base of the tail. (J287.13.w1)
  • Taken from the point of the shoulder to the point of the buttocks. (J12.59.w1)
  • Body length was measured from the base of the skull to the base of the tail. (J287.13.w1)
  • From the point of the shoulder to the tuber iscii in cm. (J2.28.w4)
  • Measure the total length excluding the trunk from the midpoint of a line drawn between the inner corners of the eyes, along the spinal ridge (with the tape flat along the skin) to the tip of the tail (end of the last tail vertebra, with the tail held out from the body). Measure the tail length from the highest point of the anal folds on either side of the tail to the end of the last tail vertebra, with the tail held out from the body. The head and body length is then calculated as total length minus tail length. (P502.1.w12)
• Shoulder height:
  • Have the elephant stand on flat ground, preferably level cement, otherwise compacted soil or clay. (P502.1.w12)
  • Place a straight pole with an attached sliding perpendicular arm next to the elephant and bring the arm to rest against the highest point of the shoulder. Note the height of the pole at this point (the pole may have measurements inscribed on it, or may be measured using a tape measure). (P502.1.w12) or
  • Sight across the elephant's shoulder to a calibrated vertical post. For accuracy, a leveling beam is laid horizontally (as indicated by a spirit level i.e. a carpenter's level) across the shoulders. Alternatively, the beam is laid across the shoulders to a vertical calibrated post on either side, the value on each side is noted and the average is taken as the height (add the two measured values and divide by two). (P502.1.w12) or
  • Balance a beam across the elephant's shoulders, using a spirit level (carpenter's level) to ensure it is horizontal. Suspend a cloth tape measure from this and read the distance to the ground, taking care that the beam is truly horizontal when the tape is read. (P502.1.w12)
  • Note: A simply-constructed apparatus for measuring elephants consists of a long vertical pole, with a sliding upper section, attached at the top to a perpendicular cross arm can be used, with a measuring tape attached along the upper section of the vertical pole and a plumb bob attached, via a short hanger, to the lower part of the vertical pole; this is used to ensure that the pole is properly vertical when the height measurement is read. (B10.49.w21)
    • Note: elephants unfamiliar with this apparatus will tend to crouch down slightly as they feel the cross arm on their shoulders, giving a height reading lower than the true value. (B10.49.w21)
  • Shoulder height may be estimated by measuring the circumference of a foot while it is weight bearing, and multiplying by two (J287.13.w1).
    • Another study found that this was approximately correct if a front foot was measured, but underestimated the height by 1.4 - 5.8% (B23. 77.w12 )
• Chest girth:
  • Wrap a measuring tape around the elephant immediately behind the front legs. Make sure the tape is totally flat, not twisted, and that it is pulled snugly around the elephant. Read the girth midway between the maximum and minimum readings obtained as the elephant breathes. (P502.1.w12)
• Neck girth:
  • Measure with a tape around the middle of the neck, pulling the tape taut to take up slack skin hanging from the neck. (P502.1.w12)
• Forefoot circumference:
  • Measure with a tape measure, round the forefoot at the widest point, starting on the lateral side of the foot. Note: This can be difficult to measure accurately, particularly in nervous animals. Measure the right fore, unless there is e.g. a toenail deformity. The same forefoot should be measured for circumference, width and length. (P502.1.w12)
• Forefoot width:
  • The maximum width should be measured using calipers. The same forefoot should be measured for circumference, width and length. (P502.1.w12)
• Forefoot length:
  • The maximum length should be measured using calipers. The same forefoot should be measured for circumference, width and length. (P502.1.w12)

Estimating body weight from linear measurements

• There are a number of weight-estimating formulae which have been developed for elephants. However, their usefulness is reduced by variations in the conformation of elephants. (B10.49.w21)
• Based on 20 elephants of various ages:
  • W (weight in kg) = 8.2g + 18.4ng - 3927 ( where g = chest girth in cm, taken just behind the elbows, and ng = neck girth, measured by tightly encircling the elephant's neck with the tape. (J12.59.w1)
  • W (weight in kg) = 12.8 (g + ng) - 4281. (J12.59.w1)
  • W = 10^-4 x 2.4313 l^.2g^2.6. (J12.59.w1)
• Two formulae provided for elephants in India: (J359.7.w3)
  • Weight in kg, W = 12.8 (g+ng) - 4281 (g = girth - chest circumference just behind the forelimb, in cm); ng = neck girth in cm). (J359.7.w3)
  • Weigh in pounds (lb) W = I x g2/300 x 1.25 (I = length from the anterior tip of the shoulder to point of hip in inches; g = girth in inches). (J359.7.w3)
• A formula for weight estimation in Indian elephants was determined as W (weight in kg) = -1010 + 0.036 x body length (in cm) x girth (in cm), where body length was measured from the base of the skull to the base of the tail and girth was measured behind the shoulder. This was calculated by measuring elephants of both sexes from several organisations in India. (J287.13.w1)
  • This formula was found in another study to underestimate weights by 32.2 - 38.6%. (B23.77.w12)
• A formula for weight estimation in domesticated Asian elephants in Sri Lanka was: y = -22.39 + 18.9x, where "y" was the shoulder height in cm and "x" the body weight in kilograms. (J350.16.w1)
  • This formula was found in another study to underestimate the weight of elephants by 9.0 - 27 %. (B23.77.w12)
• Another formula for body weight estimation in domesticated Asian elephants in Sri Lanka was calculated using the chest girth: chest girth = -60.6 + 28.9x (where x is the cube root of body weight in kg). (J350.16.w1)
  • This formula was found in another study to overestimate bodyweight by 21.2 - 52.8%. (B23.77.w12)
  • Note: American circus elephants are heavier than are Sri Lankan working elephants. (J350.16.w1, reported in (B23.77.w12))
• A study based on body measurements of 75 Asian elephants in North America (eight bulls and 67 cows, one to 57 years old, from nine herds in zoos and circuses) produced a set of regression equations to predict weight in elephants of different age classes based on girth measurements; slightly better results were obtained for most age classes by using other measurements as well. The formulae were as follows: (J2.28.w4)
  • Elephants of all ages 1 to 57 years: 18.0 × (heart girth in cm) - 3,336 = body weight in kg (R² = 0.90)
    • or 11.5 × (heart girth in cm) + 7.55 × (body length from the point of the shoulder to the tuber iscii in cm) + 12.5 × (pad circumference of a weight-bearing forefoot in cm) - 4,061 = body weight in kg (R² =94)
  • Elephants 1 to 13 years: 17.9 × (heart girth in cm) - 3,408 = body weight in kg (R² = 94).
    • or 12.4 × (heart girth in cm) + 9.33 × (body length from the point of the shoulder to the tuber iscii in cm) - 3,351 = body weight in kg (R² =0.96)
  • Elephants 18-28 years: 15.5 × (heart girth in cm) - 2,481 = body weight in kg (R² = 0.78).
    • or 11.4 × (heart girth in cm) + 6.89 × (body length from the point of the shoulder to the tuber iscii in cm) + 22.8 × (pad circumference of a weight-bearing forefoot in cm) - 5,250 = body weight in kg (R² =0.90)
  • Elephants 29-39 years: 19.4 × (heart girth in cm) - 3,786 = body weight in kg (R² = 0.78).
    • or 14.2 × (heart girth in cm) + 13.2 × (body length from the point of the shoulder to the tuber iscii in cm) - 4,662 = body weight in kg (R² =0.86)
  • Elephants 40-57 years: 20.8 × (heart girth in cm) - 4,249 = body weight in kg (R² = 0.90).

  Note: with each of these formulae, the average predicted weight closely matched the average actual weight and the average error was relatively small, however there was a considerable error range, particularly for individuals in the 1-13 year age range (-79% to + 19%) and also in the 18 - 28 year group (-30% to +13%) . (J2.28.w4)

  • The "all ages formula" was found in another study to overestimate weight by 16.5 - 41.7% while the equation based on heart girth alone for the "18 to 28 years" group produced overestimates of 9.2 - 35.4%. (B23.77.w12)
• Weight curves can be calculated for a population of elephants then used to estimate weights based on a linear measurement such as shoulder height. (J2.31.w3)
  • A study on the pharmacokinetics of oxytetracycline in Loxodonta africana - African Elephant calves of about 600 - 980 kg (estimated body weight) measured the actual shoulder heights of the calves and estimated their body weight from a semilog plot of mass in kilograms against shoulder height in centimetres, drawn previously from other calves. This study found that doses of 8.0 mg/kg or 18.0 mg/kg of a long-acting oxytetracycline preparation (Tetravet 20% LA, Kruger-Med Pharmaceutical Ltd., Park Central 2001, South Africa) gave effective serum concentrations (>0.5 µg/mL) for at least 48 hours. (J2.31.w3)

  The following data has been suggested for African elephant calves: (D301.App8.w1)

  Shoulder Height (m)	Body Mass (kg)	Shoulder Height (m)	Body Mass (kg)
  1.05 - 1.10	245	1.56 - 1.60	745
  1.11 - 1.15	275	1.61 - 1.65	810
  1.16-1.20	310	1.66 - 1.70	880
  1.21 - 1.25	355	1.71 - 1.75	950
  1.26 - 1.30	400	1.76 1.80	990
  1.31 - 1.35	440	1.81 - 1.85	1,050
  1.36 - 1.40	490	1.86 - 1.90	1,140
  1.41 - 1.45	550	1.91 - 2.00	>1,200
  1.46 - 1.50	610

The following is suggested for estimating age and mass from height for free-living elephants in South Africa: (D301.App10.w1)

Dosage calculations directly from linear measurements:

• Rather than converting linear measurements to weights for dosage calculations, dosages may be given on the basis of length measurements directly. The following is suggested: body length (from base of skull to tail head) plus girth (around the elephant just behind the front legs, or in a recumbent elephant, twice the distance from the sternum to the dorsal midline immediately behind the front legs). (J2.27.w2)
  • A study on free-ranging adult male Loxodonta africana - African Elephant concluded that therapeutic oxytetracycline concentrations could be maintained for 48 hours following a single administration of at least 58 mg/cm (sum of body length plus girth) of a long-acting oxytetracycline preparation (Tetravet 20% LA, Kruger-Med Pharmaceutical Ltd., Park Central 2001, South Africa) and recommended a dose of 60 - 80 mg/cm. (J2.27.w2)

• Physical Examination of Mammals

• For example, 100 - 300 litres per day may be required for an adult elephant with severe fluid loss due to a disease such as Salmonellosis. (B10.49.w21)
  • To deliver these volumes intravenously would require not only large quantities of sterile fluids (possibly on a daily basis for several days) but also multiple large gauge catheters and fluid pumps. (J375.1.w1)

Making up fluids:

• When large quantities of fluids are required it may be useful to use powdered electrolyte mixtures which are then made up by the gallon using distilled water. (B10.49.w21)

• This may be evaluated by considering: (B10.49.w21)
  • Packed cell volume;
  • Whether there is the normal serous dripping from the trunk;
  • How well mucous membranes are moisturised;
  • Skin turgor, which can be tested on the inside of the legs. 

  (B10.49.w21) 

• Physical Examination of Mammals